Severe COVID-19 Patients Research Articles

Impact of Laboratory Biomarkers on COVID-19 Severity: First Cross-sectional Study in a Remote Area of Pakistan

Objectives: The study aimed to evaluate the performance of rapid antigen test (RAT) and reverse transcription polymerase chain reaction (RT-PCR) in detecting COVID-19 and the impact of laboratory biomarkers on the severity of the disease. Material and Methods: A total of 150 nasopharyngeal swabs and blood samples were collected from symptomatic COVID-19 patients in Tehsil head-quarter Hospital, Dargai from August 2021 to March 2022. Results: RAT revealed a sensitivity of 86.67% and specificity of 100%, while RT-PCR revealed a sensitivity of 93.33% and specificity of 100%. The highest infection rate was found in males, and the average age of patients was 53.87 years. The most common symptoms were fever and sore throat. Patients were categorized into four groups based on cycle threshold values and blood biomarkers: mild, moderate, severe, and critical. White blood cell count, platelet count, and C-reactive protein were significantly different between the groups. Lactate dehydrogenase, D-dimer, and serum ferritin were significantly increased in critical patients. The receiver operating characteristic curve showed that inflammatory biomarkers had a comparative performance in predicting disease severity in COVID-19 patients. Conclusion: Blood biomarkers are associated with the disease severity in COVID-19 patients, and further studies, such as metabolomics, are recommended to explore the immunological mechanisms behind these biomarkers.

Risk Factors of Fungal Growth in Sputum Culture from Severe and Critical COVID-19 Patients

Patients infected with Coronavirus Disease (COVID-19), especially those with comorbidities, immunosuppressive treatment, intubated, and on ventilators, are more likely to contract fungal infection. This study aimed to describe the profile of fungal growth in sputum culture from severe and critical COVID-19 patients, and to determine the association between the fungal growth with the patient's outcome and the association between several risk factors with the fungal growth. A retrospective case-control study was carried out at Husada Utama Hospital, Surabaya. This study samples were 119 patients; fungal growth on sputum culture was seen in 64 (53.8%) patients; the three types of fungi with the highest frequency were Cryptococcus neoformans found in 23 (19.3%) patients, Candida tropicalis found in 11 (9.2%) patients and Candida dubliniensis found in 10 (8.4%) patients. There was no significant association between fungal growth and patient mortality with a p-value of 0.940 (p>0.05), also between the patient's history of diabetes mellitus and fungal growth (p=0.496) and between corticosteroid treatment and fungal growth (p=0.168). Still, there was a significant association between the use of ventilators in patients and fungal growth with a p-value of 0.001 (p<0.05). A significant association was also found between IL-6 inhibitor (Tocilizumab) treatment and fungal growth with a p-value of 0.003 (p<0.05). The most common fungi found in this study with the highest frequency was Cryptococcus neoformans. There was an association between two risk factors (the use of a ventilator and tocilizumab treatment) and fungal growth.

COVID-19 Vaccines and COVID-19 in People Living with HIV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly around the world, and COVID-19 and HIV co-infection also became common. In this study, we aimed to investigate the impact of vaccination preferences and vaccination rates on the severity of COVID-19 in patients with HIV co-infection. People living with HIV who were followed in our hospital during the COVID-19 pandemic (January 2020- December 2022) were retrospectively included in the study. The diagnosis of COVID-19 was made by detecting SARS-CoV-2 RNA in nasopharyngeal swab specimens using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Patients requiring hospital admission were classified as severe. The patient's demographics and vaccination status were collected from the hospital data system. Our study included 205 patients using antiretroviral therapy for HIV. The mean day count between the last vaccine date and SARS-CoV-2 PCR positivity was 163 days in the Comirnaty® group,149 days in the CoronaVac® group, and 154 days in the mixed-vaccinated group. Those vaccinated with Comirnaty® were statistically significantly less infected with COVID-19 after vaccination (p<0.05). The course and the outcomes of COVID-19 among SARS-CoV-2 vaccinated people living with HIV, especially with well-controlled HIV infection, seem to be similar to people living without HIV.

A Pilot and Feasibility Study to Evaluate the Effectiveness of Tofacitinib Add-On Therapy to Remdesivir in Severely Ill COVID-19 Patients.

This placebo-controlled and randomized pilot study aimed to assess the feasibility and impact of tofacitinib/remdesivir combination therapy compared to remdesivir alone on clinical and laboratory findings of severely ill COVID-19 patients for future large-scale studies. Fifty patients were included in this study. They were randomly allocated into two groups of 25 subjects each. Patients in the treatment group received a five-day course of tofacitinib (10 mg twice daily) in addition to a five-day course of remdesivir, whereas the control group received a 10-day course of remdesivir with a placebo. There was no significant difference in rates of need for intubation (oxygen saturation level), intensive care unit (ICU) admission, death and length of hospitalization between the two groups (P>0.05). Nevertheless, the PRIEST severity score was significantly reduced in the treatment group compared to the control group (P=0.03, effect size [95% CI]: -0.616 [0.0233-1.1723]). Moreover, the mean level of C-reactive protein after 10 days was significantly decreased in the treatment group but increased in the control group (P=0.006). Tofacitinib adopted in this pilot study modulate the inflammation and reduce the PRIEST score in severe COVID-19 patients. So, it is feasible and could be applied in future larger-scale trials to precisely determine its effects on coronavirus infections.

Identification of CXCL9 chemokine as a potential biomarker for assessing clinical severity in COVID-19 patients.

The severity and clinical outcome of COVID-19 depend on virus-specific factors and the host's inflammatory response. Identifying biomarkers of severe COVID-19 is a crucial condition and predicts disease severity. This study enrolled a total of 167 patients with COVID-19. These patients were categorized into three groups based on the severity of the disease: moderate course - 78 individuals, severe course - 52 individuals, and extremely severe course - 37 individuals. We analyzed chemokines (IP-10, CXCL9, CCL17) and cytokine IL28B levels using the enzyme immunoassay (EIA) method. CXCL9 levels were increased in severe and extremely severe cases compared to moderate ones. The CCL17 chemokine demonstrated significant elevation in severe cases. However, there was no significant difference in the level of IP-10, and IL28B in the compared groups. Our findings suggest that CXCL9 and CCL17 chemokines could be used as biomarkers to assess the clinical status of patients with COVID-19 and can relate to disease severity. These biomarkers could aid in identifying patients at high risk for severe disease and help guide clinical decision-making for the effective management of COVID-19.

Predictive value of D-Dimer and thromboplastin time as coagulation indicators for COVID-19 patients.

Coronavirus 2019 symptoms include coagulopathy and thromboembolic risk. Using one parameter to diagnose coagulopathy has little predictive value. This study will examine if D-dimer and APTT testing can predict COVID-19 severity and aid triage and manage patients. 214 COVID-19 patients were enrolled and classified into two categories based on their respiratory manifestations; mild (126 cases) and severe (88 cases). Patient data regarding age, gender, D-Dimer level, and APTT level were collected. When both D-Dimer and APTT levels were abnormal, in this study, the patient was considered to have a coagulation disorder. Indicators of coagulation in the COVID-19 patients were collected and compared between the two groups. Chi-square (χ2) tests were used to determine the significant differences between coagulation disorders in the two groups. Our findings showed that patients with coagulopathies were more likely to belong to the severe group. Within the two groups of patients, the rate of coagulation disorders was as follows: mild = 8.8 % within coagulation disorders, 4.8% within the two Groups; severe = 91.2 % within coagulation disorders, 77.8 % within the two Groups. There was a statistically significant relationship between coagulation disorder and severe COVID-19 patients compared to mild patients (p < 0.05). Coagulation disorders are more likely to occur in severe COVID-19 patients. D-Dimer and APTT tests are significant indicators for predicting COVID-19 severity. Our research found an abnormal pattern of coagulation disorders and COVID-19 severity that should be considered in the COVID-19 treatment protocol.

Impact of the long-term hydroxychloroquine use on COVID-19 severity in patients with autoimmune rheumatic disease

Background-Aim: After the numerous studies, the clinical effectiveness of hydroxychloroquine (HCQ) against SARS-CoV-2 is now accepted limited. Besides this, HCQ has still been the first option in most rheumatology practices. To evaluate the frequency, severity and complication of COVID-19 in patients with autoimmune rheumatologic disease (ARD) receiving and not receiving long-term HCQ. Methods: A total of 309 ARD patients were retrospectively evaluated for COVID-19 disease with a SARS-CoV-2 RT-PCR and IgM/IgG antibody.Patients were grouped as HCQ or non-HCQ groups. COVID-19 clinical symptoms development of viral pneumonia, rates of hospitalization, mortality due to COVID-19 and time from initial symptom to viral pneumonia, clinical recovery and RT-PCR negativity were evaluated. Results: During the 13 month study period, 54 (17.4%) were diagnosed with COVID-19, the frequency of COVID-19 was similar between the HCQ (17.9%) and non-HCQ groups (16.7%), p=0.793. The frequency of the myalgia, arthralgia and sore throat were higher in the non-HCQ group, the frequency of other clinical signs and symptoms were higher in the HCQ group but none of them reached statistical significance. In all patients, viral pneumonia was diagnosed in 9 (16.7%), requiring hospitalization in 8 (14.8%), requiring oxygen therapy in 4 (7.4 %) patients and these severe COVID-19 clinical features were similar between groups. COVID-19 complications were seen in 2 patients, 1 of whom was mortality due to ARDS and one was supraventricular tachycardia but thromboembolism or rheumatologic disease activation were not observed. Conclusions: As with the frequency of COVID-19, severity of COVID19 were similar between patients with and without long-term HCQ use in ARD. COVID 19 complications were found to be rare in our study.

Intravenous high-dose anakinra drops venous thrombosis and acute coronary syndrome in severe and critical COVID-19 patients: a propensity score matched study

In our study, we aimed to evaluate the effect of high-dose intravenous anakinra treatment on the development of thrombotic events in severe and critical COVID-19 patients. This retrospective observational study was conducted at a tertiary referral center in Aksaray, Turkey. The study population consisted of two groups as follows; the patients receiving high-dose intravenous anakinra (anakinra group) added to background therapy and the patients treated with standard of care (SoC) as a historical control group. Age, gender, mcHIS scores, and comorbidities such as diabetes mellitus, hypertension, and coronary heart disease of the patients were determined as the variables to be matched. We included 114 patients in SoC and 139 patients in the Anakinra group in the study. Development of any thromboembolic event (5% vs 12.3%, p = 0.038; OR 4.3) and PTE (2.9% vs 9.6%, p = 0.023; OR 5.1) were lower in the Anakinra group than SoC. No patient experienced cerebrovascular accident and/or clinically evident deep venous thrombosis both in two arms. After 1:1 PS matching, 88 patients in SoC and 88 patients in the Anakinra group were matched and included in the analysis. In survival analysis, the development of any thromboembolic event, pulmonary thromboembolism, and acute coronary syndrome (ACS) were higher in SoC compared to Anakinra. Survival rate was also lower in patients with SoC arm than Anakinra in patients who had any thromboembolic event as well as ACS. In our study, the development of thrombosis was associated with hyperinflammation in patients with severe and critical COVID-19. Intravenous high-dose anakinra treatment decreases both venous and arterial events in patients with severe and critical COVID-19.

APOBEC3-related mutations in the spike protein-encoding region facilitate SARS-CoV-2 evolution

SARS-CoV-2 evolves gradually to cause COVID-19 epidemic. One of driving forces of SARS-CoV-2 evolution might be activation of apolipoprotein B mRNA editing catalytic subunit-like protein 3 (APOBEC3) by inflammatory factors. Here, we aimed to elucidate the effect of the APOBEC3-related viral mutations on the infectivity and immune evasion of SARS-CoV-2. The APOBEC3-related C > U mutations ranked as the second most common mutation types in the SARS-CoV-2 genome. mRNA expression of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) in peripheral blood cells increased with disease severity. A3B, a critical member of the APOBEC3 family, was significantly upregulated in both severe and moderate COVID-19 patients and positively associated with neutrophil proportion and COVID-19 severity. We identified USP18 protein, a key molecule centralizing the protein-protein interaction network of key APOBEC3 proteins. Furthermore, mRNA expression of USP18 was significantly correlated to ACE2 and TMPRSS2 expression in the tissue of upper airways. Knockdown of USP18 mRNA significantly decreased A3B expression. Ectopic expression of A3B gene increased SARS-CoV-2 infectivity. C > U mutations at S371F, S373L, and S375F significantly conferred with the immune escape of SARS-CoV-2. Thus, APOBEC3, whose expression are upregulated by inflammatory factors, might promote SARS-CoV-2 evolution and spread via upregulating USP18 level and facilitating the immune escape. A3B and USP18 might be therapeutic targets for interfering with SARS-CoV-2 evolution.

#2395 Elevated circulating ACE2 activity is related with a major COVID-19 severity

Abstract Background and Aims The angiotensin 2 converser enzyme (ACE2) is the cell entry receptor for SARS-CoV-2. SARS-CoV2 participates in ACE2 shedding from cell membrane, increasing soluble ACE2. The present study aims to evaluate if ACE2 serum levels are to COVID-19 prognosis. Method During the first wave of COVID-19 pandemic and during March and April 2020, 2118 first emergency attendance serum samples from diagnosed COVID-19 patients from Barcelona Vall d'Hebron Hospital were obtained. Age, sex, previous comorbidities, clinical and analytical variables were collected from the patient clinical records. Patients that were admitted to ICU, required mechanical ventilation or died due to COVID-19 were considered severe patients. Serum ACE2 activity was measured by enzymatic activity assay. Results Patients with severe COVID-19 were older and with a major number of comorbidities (Table 1). Circulating ACE2 activity at admission was increased in 0.34 relative fluorescence units (RFUs)/ng/μL (CI 95%: 0.24-0.43, p &amp;lt; 0.001) in patients that developed severe COVID-19. A logistic regression model adjusted by age, sex, diabetes, hypertension, obesity, cardiovascular disease, chronic kidney disease and renin angiotensin blockers, showed that high circulating ACE2 activity was still related to a worse prognosis (OR: 2.0, 95% CI: 1.7–2.4, p &amp;lt; 0.001). High serum ACE2 activity ≥0.56 RFU/ng/μL provided the best sensitivity (62%) and specificity (61%) relation, whereas values ≥1.3 RFU/ng/μL were significantly related to a worse prognosis of the disease with a 95% specificity. Conclusion High levels of circulating ACE2 activity when patients with COVID-19 are admitted to the Emergency Department are independently related with a subsequent severe disease. Additionally, although most of the comorbidities analyzed are significantly increased in severe COVID-19 patients as compared to mild COVID-19 patients, the results of the logistic regression model point out that they seem not to be a risk factor in the overall model, except for obesity, age and sex.

The Interleukin-6 gene variants may protect against SARS-CoV-2 infection and the severity of COVID-19: a case-control study in a Moroccan population

The symptoms of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to severe forms marked by acute respiratory distress syndrome, multi-organ damage, and fatalities. Studies indicate a correlation between specific genes and susceptibility to SARS-CoV-2 infection and disease severity, particularly involving variants in genes linked to inflammation and immune responses. The objective of this study is to investigate the association between rs1800795 (− 174 G > C) and rs1800797 (− 597 A > G) variants in the interleukin-6 (IL-6) promoter region and susceptibility to SARS-CoV-2 infection. Additionally, we aim to explore their correlation with COVID-19 severity in a Moroccan population. In this case-control study, we enrolled 270 unvaccinated COVID-19 patients, consisting of 132 with severe COVID-19 and 138 with asymptomatic-moderate COVID-19. Additionally, we included 339 SARS-CoV-2-negative group. Genotyping of rs1800795 and rs1800797 polymorphisms of the IL-6 gene was performed using predesigned TaqMan SNP genotyping. The median age of SARS-CoV-2-negative controls was 50 years, while severe COVID-19 cases exhibited a median age of 61 years. Additionally, individuals with asymptomatic to moderate COVID-19 had a median age of 36 years. We observed a significant age difference between severe and mild COVID-19 patients (p < 0.0001), and an association was noted between gender and the severity of COVID-19 (p = 0.011). The allele and genotype frequencies of the IL-6 − 597G > A and − 174G > C variants did not show significant associations with susceptibility to SARS-CoV-2 infection (p > 0.05). However, further analysis revealed that the linkage disequilibrium between rs1800797 and rs1800795 indicated that individuals with the GC* haplotype (OR = 0.04, 95% CI 0.01–0.30, p = 0.001) and AG* haplotype (OR = 0.11, 95% CI 0.03–0.46, p = 0.002) were significantly associated with protection against SARS-CoV-2 infection. Moreover, in the overdominant model, the IL-6 − 174 G/C genotype was found to be protective against the development of severe disease compared to those with the G/G-C/C genotypes (p = 0.03; OR = 0.41, 95% CI 0.18–0.96). However, correlations between complete blood count markers, hematological markers, D-dimer, C-reactive protein, and ferritin levels according to − 597 A > G and − 174G > C genotypes showed no significant differences (all p > 0.05). Our findings provide valuable insights into the pathogenesis of COVID-19, suggesting that genetic variations at the IL-6 gene may contribute to the susceptibility to severe SARS-CoV-2 infection within the Moroccan population.

Clinical Outcomes among Hospitalized COVID-19 Patients Who Received Baricitinib or Tocilizumab in Addition to Standard of Care.

COVID-19 infection is caused by the novel severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). This novel virus has transformed into different resistant variants (e.g., omicron; delta; alpha; epsilon) since its first emergence in 2019. The National Institutes of Health and Infectious Diseases Society of America guidelines currently recommend adding either baricitinib or tocilizumab to the standard of care for severe COVID-19 treatment. An outcome comparison between baricitinib and tocilizumab is needed to determine which agent is more appropriate and safer in clinical practice when deciding treatment. We aimed to compare mortality and clinical outcomes between tocilizumab and baricitinib in the management of severe COVID-19 infection. A total of 5638 adult patients from 16 acute care hospitals in a large healthcare system in Texas were included in this multicentered retrospective cohort study. The median age of the patients was 56 years and 46.67% of them were female. Severe COVID-19 patients were treated with standard of care and either tocilizumab or baricitinib. The primary outcome of hospital admission mortality rates was found to be higher with tocilizumab (odd ratio (OR) of 1.56; p = 0.001; 95% CI 1.19 to 2.008) compared to that with baricitinib (OR 0.65; p = 0.001; 95% CI 0.50 to 0.84). For one of the secondary outcomes, patients who received tocilizumab were 3.75 times more likely to be admitted to the ICU than those receiving baricitinib (p = 0.001; 95% CI 2.89 to 4.85). Among the 1199 COVID-19 patients who were admitted to the ICU, the ICU length of stay was shorter among patients receiving baricitinib with a mean difference of 4.42 days and a median difference of 2.54 days, compared to those receiving tocilizumab (p < 0.0001; 95% CI -5.97 to -2.62) as another secondary outcome. Our large retrospective observational study showed that baricitinib reduced mortality; the likelihood of ICU admission; and the ICU length of stay compared to tocilizumab in patients with severe COVID-19 infection.

Surveying haemoperfusion impact on COVID-19 from machine learning using Shapley values.

Haemoperfusion (HP) is an innovative extracorporeal therapy that utilizes special cartridges to filter the blood, effectively removing pro-inflammatory cytokines, toxins, and pathogens in COVID-19 patients. This retrospective cohort study aimed to assess the clinical benefits of HP for severe COVID-19 cases using Shapley values for machine learning models. The research involved 578 inpatients (≥ 20years old) admitted to Baqiyatallah hospital (Tehran, Iran). The control group (359 patients) received standard treatment, including high doses of corticosteroids (a single 500mg methylprednisolone pulse, followed by 250mg for 2days), categorized as regimen (I). On the other hand, the HP group (219 patients) received regimen II, consisting of the same corticosteroid treatment (regimen I) along with haemoperfusion using Cytosorb H300. The frequency of haemoperfusion sessions varied based on the type of lung involvement determined by chest CT scans. In addition, the value function defines the Shapley value of the th feature for the query point , where the input matrix features represent individual characteristics, drugs, and history and clinical conditions of the patient. Our data showed a favorable clinical response in the HP group compared to the control group. Notably, one-to-three sessions of HP using the CytoSorb® 300 cartridge led to reduced ventilation requirements and mortality rates in severe COVID-19 patients. Shapley values were calculated to evaluate the contribution of haemoperfusion among other factors, such as side effects, medications, and individual characteristics, to COVID-19 patient outcomes. In addition, there is a significant difference between the two groups among the treatments and medications used remdesivir, adalimumab, tocilizumab, favipiravir, Interferon beta-1a, enoxaparin prophylaxis, enoxaparin full dose, heparin prophylaxis, and heparin full dose (P < 0.05). It seems that haemoperfusion has a positive impact on the reduction of inflammation markers and renal functional such as ferritin and creatinine, respectively, as well as D-dimer and WBC levels in the HP group were significantly lower than the control group. The findings indicated that haemoperfusion played a crucial role in predicting patient survival, making it a significant feature in classifying patients' prognoses.

Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients

BackgroundA 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented.ResultsTo analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001).ConclusionsBy using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Potential Role of Inflammasome NLRP3 and IL-1β Gene Expression in COVID-19 Patients: Impact of Ferritin and D –Dimer

Dysregulated inflammation and hypercoagulability underlie the development of severe illness in COVID-19. Biomarkers related to inflammasome activation, including interleukin (IL)-1β and NLRP3, and inflammatory lung cytokine as IL-8. As well as coagulation markers like D-dimer. The aim of this study was to identify associations between the dysregulated immune response biomarkers and the severity of the disease that will help in prognostic and potential therapeutic utility. Twenty five mild/moderate and 25 severe COVID-19 patients were included in this study as well as 25 healthy controls. Survival analysis was done after follow up for one month. Inflammasome (IL-1β, NLRP3), lung cytokine (IL-8), and vitamin D levels were analyzed by real time PCR and ELISA. The mRNA expression levels of IL-1β , NLRP3 and serum level of IL-8 were elevated in cases than controls. COVID-19 patients exhibited lower levels of vitamin D. The severe group showed significant higher levels of D dimer and ferritin. Correlation analyses indicated associations between IL-1β , NLRP3, IL-8, D-dimer and ferritin. ROC curve analyses demonstrated the potential of IL-1β , NLRP3 and IL-8 in distinguishing between mild/moderate and sever cases. Survival analyses indicated a link between high levels of IL-1β , NLRP3 and IL-8 with decreased survival.. The inflammasome appears pivotal in orchestrating detrimental hyperinflammation in severe COVID-19. IL-1β holds particular potential as a prognostic indicator of poor outcomes. In the future, the possible using of these biomarkers inhibitors may improve survival , decrease severity and improve management of the cases.

Determinants of post-acute COVID-19 syndrome among hospitalized severe COVID-19 patients: A 2-year follow-up study.

Post-acute COVID-19 syndrome is a condition where individuals experience persistent symptoms after the acute phase of the COVID-19 infection has resolved, which lowers their quality of life and ability to return to work. This study assessed the prevalence and associated risk factors of post-acute COVID-19 syndrome (PACS) among severe COVID-19 patients who were discharged from Millennium COVID-19 Care Center, Addis Ababa, Ethiopia. A cross-sectional study using data collected from patient charts and a follow-up telephone interview after two years of discharge. Systematic random sampling was used to select a total of 400 patients. A structured questionnaire developed from the case report form for PACS of the World Health Organization (WHO) was used. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression. Out of the 400 patients, 20 patients were dead, 14 patients refused to give consent, and 26 patients couldn't be reached because their phones weren't working. Finally, 340 were included in the study. The majority (68.5%) were males and the mean age was 53.9 (±13.3 SD) years. More than a third (38.1%) of the patients reported the persistence of at least one symptom after hospital discharge. The most common symptoms were fatigue (27.5%) and Cough (15.3%). Older age (AOR 1.04, 95% CI 1.02-1.07), female sex (AOR 1.82, 95% CI 1.00-3.29), presence of comorbidity (AOR 2.38, 95% CI 1.35-4.19), alcohol use (AOR 3.05, 95% CI 1.49-6.26), fatigue at presentation (AOR 2.18, 95% CI 1.21-3.95), and longer hospital stay (AOR 1.06, 95% CI 1.02-1.10) were found to increase the odds of developing post-acute COVID-19 syndrome. Higher hemoglobin level was found to decrease the risk of subsequent post-acute COVID-19 syndrome (AOR 0.84, 95% CI 0.71-0.99). The prevalence of post-acute COVID-19 syndrome is high, with a wide range of persistent symptoms experienced by patients. COVID-19 survivors with the identified risk factors are more susceptible to post-acute COVID-19 and require targeted monitoring and care in a multidisciplinary approach.

Serum Adiponectin Predicts COVID-19 Severity.

Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general.

Immune response variation in mild and severe COVID-19 patients.

Sixty patients with COVID-19 infection were categorized into mild and severe groups, and their immune response was analyzed using flow cytometry and complete blood count. An observed increase in immune activation parameters, notably a higher percentage of CD4 lymphocytes co-expressing CD69 and CD25 molecules, and enhanced activity of the macrophage-monocyte cell line was noted in the mild group. Although Group 2 (severe COVID) had fewer CD4 cells, significant migration and proliferation were evident, with increased CD4CD69, CD8 HLA-DR+, and CD8CD69 lymphocytes. The CD4 to CD8 ratio in Group 1 suggested potential autoimmune reactions, while Group 2 indicated potential immunosuppression from severe infection and employing immunosuppressive drugs. Additionally, Group 2 exhibited an increased neutrophil count, hinting at possible bacterial co-infection. Group 1 showed differences in CD4RO and CD8RA lymphocyte populations, implying that cellular immunity plays a role in developing efficient postinfectious immunity. This intimation suggests that vaccination might mitigate the severity of the coronavirus infection and prevent complications, including long-term COVID-19.

Frequency and factors associated with severe COVID-19 patients.

Objective: To determine the frequency and factors leading to the development of severe COVID-19 in patients presenting at civil hospital, Karachi. Study Design: Cross-sectional study. Setting: Department of Medicine, Dr. Ruth K.M Pfau Civil Hospital, Karachi. Period: July 16, 2021 to January 15, 2022. Methods: Patients of age 20 to 80 years of either gender and presented with fever (&gt;38°C) for more than three days and diagnosed COVD-19 on PCR were included. Severity and factors of the disease were assessed and noted by researcher on pre-designed proforma. Results: The mean age was 48.5±11.07 years and most of the patients were males (56.7%) and urban residents (67%). Out of 97 COVID-19 patients, 12 had severe COVID-19 disease (12.4%), while 85 patients had mild to moderate COVID-19 disease (87.6%). In distribution of factors leading for development of severe covid-19, increasing age was noted in 8 (66.7%) patients, chronic kidney disease in 4 (33.3%), diabetes mellitus type II 3(25.0%), hypertension 6(50.0%), smoking 3 (25.0%), heart failure 2 (16.7%) while anemia was noted in 1 (8.3%) patient. Of 12 severe COVID-19 patients, 8 patients had positive family history of COVID-19. There was statistically significant association between COVID-19 severity and family history of COVID-19 (p=0.001). Conclusion: Severe covid-19 is common in patients presenting with fever while increasing age was noted as most common factor leading to development of severe covid-19 followed by hypertension and diabetes mellitus.

Comparing vitamin D receptor gene polymorphisms in rs11568820, rs7970314, rs4334089 between COVID-19 patients with mild and severe symptoms: a case control study

The associations of vitamin D receptor (VDR)- single nucleotide polymorphisms (SNPs) with the symptoms of COVID-19 may vary between patients with different severities of COVID-19. Therefore, in the present study, we aim to compare VDR polymorphisms in severe and mild COVID-19 patients. In this study, a total number of 85 hospitalized patients and 91 mild/moderate patients with COVID-19 were recruited. SNPs in VDR genes were determined using ARMS and then confirmed by sanger sequencing. The mean (SD) age of participants in hospitalized and non-hospitalized group was 59.0 (12.4) and 47.8 (14.8) years, respectively. Almost 46% of participants in hospitalized and 48% of participant in non-hospitalized group were male. The frequency of TT genotype of SNP rs11568820 was significantly lower in hospitalized than non-hospitalized group (3.5% vs. 17.6%; P = 0.018). However, there was no significant differences between genotypes of SNPs rs7970314 and rs4334089 and also alleles frequencies in all SNPs of two groups. The genotype of rs11568820 SNP had an inverse association with hospitalization of patients with COVID-19 after adjustment for comorbidities [OR 0.18, 95% CI 0.04, 0.88; P = 0.034]. While, there was no relationship between genotypes of SNPs rs7970314 and rs4334089 and hospitalization. The TT genotype of rs11568820 plays protective role in sever COVID-19 and hospitalization. Further studies with a large sample size which consider various confounding factors are warranted to confirm our results.