Severe COVID-19 Research Articles

The Association Between COVID-19 Infection Severity and Micronutrient Deficiencies in Children

Background: Coronavirus disease 2019 (COVID-19) can cause pulmonary and systemic inflammation in both children and adults. Investigating the potential impact of micronutrient deficiencies on COVID-19 infection is of great importance. Objectives: This case-control study was designed to compare the serum levels of vitamins D and C and zinc between healthy children and children with mild or severe COVID-19 infection, as well as to investigate the impact of micronutrient deficiencies on the clinical symptoms of patients. Methods: This case-control study was conducted at a teaching hospital in Tehran, Iran. Control subjects were recruited from healthy children, and cases were included from children with mild and severe symptoms of COVID-19. Blood samples were obtained from participants to measure the levels of micronutrients and were analyzed using statistical software. Results: A total of 85 subjects were included (33 controls, 25 cases with mild symptoms, and 27 cases with severe symptoms). We found no differences in the means of serum vitamin D and vitamin C levels between the studied groups. However, the mean serum zinc level was significantly lower in severe patients compared to the controls (P < 0.01). Moreover, no significant difference was observed in the frequency of patients with micronutrient deficiencies based on their clinical conditions. Conclusions: Our findings revealed zinc deficiency in children with severe COVID-19 infection, while no significant differences were found in the mean serum levels of vitamins D and C between healthy children and patients. More studies are necessary to provide more robust evidence.

Immediate and long-term consequences of coronavirus disease 2019 on fertility and androgenic status of men

BACKGROUND: The new coronavirus disease 2019 (COVID-19) recognized as a global pandemic, impacts many human organs and systems. In view of the coronavirus widespread and high incidence of the disease in young men of reproductive potential, It would be relevant to assess the immediate and long-term consequences of coronavirus disease on the reproductive system of men and their hormonal status AIM: To study of the effect of COVID-19 on the male reproductive system and hormonal status. MATERIALS AND METHODS: The study included the findings of examination and treatment of 62 men aged 22 to 45 years (mean age: 38.3 ± 3.2 years) who had COVID-19 confirmed by PCR testing within 3-6 months prior to the study. Sixteen (25.8%) men had severe disease, and 46 (74.2%) men suffered from moderate one. All patients enrolled in the study had spermogram parameters, mixed antiglobulin reaction (MAR) test findings and total plasma testosterone levels were within the reference values before the disease. These parameters were determined for all patients after recovery at 6 and 12 months. RESULTS: Six months after the disease, significant spermatogenesis disorders, manifested by a decreasing concentration and/or mobility and/or the number of normal forms of spermatozoa, leukospermia, were observed in 14 of 16 (87.5%) patients in the severe disease group and in 16 of 46 (34.7%) patients with moderate severity disease (p 0.05). Total plasma testosterone levels were decreased in all 16 (100%) patients in the severe group and in 32 of 46 (69.6%) patients in the moderate group (p 0.05). Within 12 months after the disease, significant disorders in the main spermogram parameters were observed in 5 of 16 (31.2%) patients with severe coronavirus disease, and in 4 of 46 (8.7%) patients with moderate coronavirus (p 0.05). A decrease in total plasma testosterone levels occurred in 10 of 16 (62,5%) men of the severe disease group and in 4 of 46 (8.7%) men with moderate disease (p 0.05). CONCLUSIONS: Our findings demonstrate the negative impact of COVID-19 on male fertility and hormonal status. The coronavirus severity mainly determines the rate, intensity and duration of spermatogenesis disorders and hypogonadism manifestations that occur after it.

Possible Link between Gut Microbiota, Diet, and COVID-19 Infection

Background: Coronavirus disease 2019 (COVID-19) is a concern for world health since it may impact both the upper (nose, throat, sinuses) and lower (trachea, lungs) respiratory tracts. Death (at a rate of 10%), respiratory failure, multi-organ failure, and acute respiratory distress syndrome (ARDS) are among the problems that might arise. Recent years have seen a global spread of zoonotic coronaviruses, which have caused human epidemics such as MERS and SARS. Various clinical symptoms may be seen in this sickness because to the numerous changes in intestinal homeostasis caused by SARS-CoV-2. Because of the beneficial impact that probiotics have on the host immune system, gastrointestinal disorders may now be effectively treated. This article discusses the close relationship between what we eat, the bacteria in our gut, and the risk of contracting the COV-19 virus. Conclusion: The relationship between gut microbiota, dietary factors, and COVID-19 severity indicates that the microbiome may influence immune regulation. Imbalances in microbial communities and reduced diversity can intensify inflammation, potentially worsening COVID-19 outcomes. Strategies such as probiotics, prebiotics, and dietary changes might provide therapeutic benefits by improving gut health and strengthening immune defenses. However, further research is required to clarify these mechanisms and establish effective interventions.

COVID-19 in children with somatic pathology

The coronavirus infection is a pressing issue in modern healthcare, yet the characteristics of the SARS-CoV-2 infection course in children with comorbidities remain insufficiently studied. The aim of this study was to evaluate the clinical form, severity, and duration of SARS-CoV-2 virus shedding in pediatric patients with somatic diseases, depending on the comorbid pathology. Materials and Methods. A comprehensive single-center retrospective study was conducted, analyzing 314 medical records of patients hospitalized in the infectious diseases department of the Russian Children’s Clinical Hospital in Moscow over 11 months in 2022. The inclusion criterion was the presence of a laboratory-confirmed COVID-19 diagnosis. Results. Children with comorbidities were found to be predisposed to a more severe course of SARS-CoV-2 infection compared to the pediatric population in general. Children with hematological diseases were at the highest risk of adverse outcomes from COVID-19. Patients with oncological and hematological diseases and primary immunodeficiencies shed the SARS-CoV-2 virus significantly longer than patients with other somatic pathologies. The duration of SARS-CoV-2 RNA detection in patients with severe COVID-19 was significantly longer, which also correlated with the severity of the underlying somatic disease. Conclusion. Children with comorbidities are at risk for a more severe and prolonged course of SARS-CoV-2 infection.

Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19.

The COVID-19 pandemic caused by the SARS-CoV-2 virus was arguably one of the worst public health disasters of the last 100 years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic-causing agents, SARS-CoV-2 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host-pathogen interaction evolved, subsequent variants of SARS-CoV-2 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host-pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID-19 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID-19 disease.

Blood CD45+/CD3+ lymphocyte-released extracellular vesicles and mortality in hospitalized patients with coronavirus disease 2019.

The global pandemic of coronavirus disease 2019 (COVID-19) represented a major public health concern. Growing evidence shows that plasma of COVID-19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID-19 patients during hospitalization and its relation to mortality risk. cEVs were quantitatively and phenotypically analysed in hospitalized non-surviving COVID-19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation. Levels of cEV subtypes differed between patients with severe COVID-19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan-leukocyte, and lung epithelial cell-shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2-positive eEVs were significantly increased before death compared to admission whereas endoglin and E-selectin-containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell-derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+-ℓEVs were significantly associated to the patient's survival time. An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell-derived EVs in COVID-19 pathogenesis.

Factors Predicting COVID-19 Vaccine Effectiveness and Longevity of Humoral Immune Responses

The COVID-19 pandemic, caused by SARS-CoV-2, prompted global efforts to develop vaccines to control the disease. Various vaccines, including mRNA (BNT162b2, mRNA-1273), adenoviral vector (ChAdOx1, Ad26.COV2.S), and inactivated virus platforms (BBIBP-CorV, CoronaVac), elicit high-titer, protective antibodies against the virus, but long-term antibody durability and effectiveness vary. The objective of this study is to elucidate the factors that influence vaccine effectiveness (VE) and the longevity of humoral immune responses to COVID-19 vaccines through a review of the relevant literature, including clinical and real-world studies. Here, we discuss the humoral immune response to different COVID-19 vaccines and identify factors influencing VE and antibody longevity. Despite initial robust immune responses, vaccine-induced immunity wanes over time, particularly with the emergence of variants, such as Delta and Omicron, that exhibit immune escape mechanisms. Additionally, the durability of the humoral immune responses elicited by different vaccine platforms, along with the identification of essential determinants of long-term protection—like pre-existing immunity, booster doses, hybrid immunity, and demographic factors—are critical for protecting against severe COVID-19. Booster vaccinations substantially restore neutralizing antibody levels, especially against immune-evasive variants, while individuals with hybrid immunity have a more durable and potent immune response. Importantly, comorbidities such as diabetes, cardiovascular disease, chronic kidney disease, and cancer significantly reduce the magnitude and longevity of vaccine-induced protection. Immunocompromised individuals, particularly those undergoing chemotherapy and those with hematologic malignancies, have diminished humoral responses and benefit disproportionately from booster vaccinations. Age and sex also influence immune responses, with older adults experiencing accelerated antibody decline and females generally exhibiting stronger humoral responses compared to males. Understanding the variables affecting immune protection is crucial to improving vaccine strategies and predicting VE and protection against COVID-19.

Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19.

While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. "In vitro" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis.

Identifying COVID-19 variant through symptoms profile: Would it be possible? A rapid review.

The first outbreaks of coronavirus CoV, SARS-CoV and MERS-CoV have occurred in China and Saudi Arabia over the past decade, respectively. From the end of 2019, a great battle began by the world scientific community against SARS-CoV-2, the virus that caused COVID-19, a pathology that generated devastating consequences on all existing continents. Several mutations have already been detected in the structure of the virus, which have been responsible for the generation of many types of variants since the detection of the first COVID-19 virus identified in China. The worrisome mutations arising from the first genome of SARS-CoV-2 have been intensively studied. Some mutations increase the transmissibility of the disease through Spike, the protein responsible for binding the virus in the human cell. Among the numerous strains, the most discussed are called by the WHO as "variants of concern". This study aims to review if COVID-19 severity may be variant dependent. Our study found tree publications that associate severity of COVI-19 symptoms to different SARS-CoV-2 variants. The most part of publications do not establish which variant is being expressed during studies. More studies with this focus are needed for a better understanding of the disease and respective variants.

DIABETES MELLITUS TIPO 2 COMO FATOR DE RISCO PARA O AGRAVO DA COVID-19 NA POPULAÇÃO BRASILEIRA: UMA REVISÃO SISTEMÁTICA

INTRODUCTION: The novel coronavirus, named SARS-CoV-2, is the etiological agent of COVID-19, a highly contagious infectious disease that primarily affects the lower respiratory tract. Type 2 diabetes mellitus may be a factor worsening this condition. OBJECTIVE: To identify the prevalence of diabetes mellitus as a risk factor for COVID-19 in Brazil from 2019 to 2023, assess the severity of cases in different states, analyze the sociodemographic factors affecting prognosis, and clarify the role of pharmacists in monitoring and managing the therapy of these patients. METHODOLOGY: This is a systematic review study using the PRISMA method, divided into four stages. The first stage involved searching for scientific works to answer the question about the frequency of worsening COVID-19 cases associated with type 2 diabetes mellitus in Brazil. The databases consulted were Scielo, PubMed, and the Virtual Health Library (BVS), using keywords such as “Diabetes mellitus,” “COVID-19,” “Brazil,” “Worsening,” and “Death.” RESULTS: Seveteen articles that met the inclusion criteria were selected. The studies indicate that diabetes mellitus is a significant risk factor for the severity and mortality of COVID-19 in Brazil, with mortality rates between 40% and 55% among diabetic patients. Additionally, the disease is associated with other comorbidities, such as hypertension and obesity, contributing to the need for ICU admissions and longer hospital stays. CONCLUSION: Type 2 diabetes mellitus is a significant risk factor for complications and mortality in COVID-19 patients, resulting in higher ICU admission rates and deaths, highlighting the need for rigorous glycemic control. The pharmacist's role is essential in monitoring glycemic levels and educating patients about treatment, contributing to reducing complications and improving clinical outcomes.

Evolving COVID-19 Landscape: Assessing the Effectiveness and Safety Profile of Nirmatrelvir/Ritonavir in Adolescents

This study evaluates nirmatrelvir/ritonavir (Paxlovid) in preventing severe coronavirus disease 2019 in adolescents (12–18). Conducted from January 2022 to July 2023, it compared hospital admissions and healthcare visits within 30 days post-treatment. Results showed similar follow-up rates between treated and untreated groups, with slightly more adverse effects in the nirmatrelvir/ritonavir group. Further research is needed to confirm its efficacy in this population.

Cushing's syndrome and COVID-19.

This review aims to present current data on the course of COVID-19 in patients with Cushing syndrome (CS) and discuss treatment for CS during to the pandemic. Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Cushing syndrome", "Hypercortisolism" and "Glucocorticoid". Chronic hypercortisolism has been reported to increase infectious risk and worsens prognostic of patients with COVID-19 potentially due to its direct impact on the immune system: lymphopenia, impairment of monocytes and neutrophils activity, diminution of complement activation. Main metabolic complications of CS - i.e. diabetes, hypertension and obesity - have been recognized as COVID-19 complications risk factors. Patients with CS treated with steroidogenesis inhibitors might experience adrenal insufficiency during COVID-19. Special attention should be paid to patients with CS and COVID-19. The pandemic has impacted - and delayed - care of chronic illnesses including CS. Specific recommendations had been provided during the pandemic: favor telemedicine consultations, limit in-hospital explorations and postpone surgery when feasible. There are enough evidence for an increased prevalence and severity of COVID-19 to recommend a specific attention and caution in patients with CS.

Comprehensive Code List Associated with Underlying Medical Conditions Identified by the CDC as High-Risk Factors for Progression to Severe COVID-19 Outcomes

Comprehensive Code List Associated with Underlying Medical Conditions Identified by the CDC as High-Risk Factors for Progression to Severe COVID-19 Outcomes

Humoral response 24 months after the first COVID-19 vaccination in people with HIV with and without diabetes

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

The Protective Role of the Ratio of Arterial Partial Pressure of Oxygen and Fraction of Inspired Oxygen after Re-Supination in the Survival of Patients with Severe COVID-19 Pneumonia

The Protective Role of the Ratio of Arterial Partial Pressure of Oxygen and Fraction of Inspired Oxygen after Re-Supination in the Survival of Patients with Severe COVID-19 Pneumonia

Relationship between Concentrations of Oxygen and Levels of Oxidative Stress in Patients Receiving Oxygen Therapy for Severe COVID-19 Pneumonia

Relationship between Concentrations of Oxygen and Levels of Oxidative Stress in Patients Receiving Oxygen Therapy for Severe COVID-19 Pneumonia

Subjective well-being and mental health during the COVID-19 pandemic in Hungary

Purpose This study aims to examine the impact of COVID-19 pandemics on subjective well-being (SWB) and mental health in Hungary, with a particular focus on the roles of socioeconomic and COVID-19-related factors in shaping these outcomes. Design/methodology/approach A cross-sectional online survey was conducted among 2,000 Hungarian adults from May 25 to June 8, 2021. The data was collected using standardized questionnaires, including the SWLS, GAD-7 and PHQ-9. Correlation analysis, one-way ANOVA and linear regression were used. Findings The study found significant anxiety (41.5%), depression (48.1%) and life dissatisfaction (41.9%) among 2,000 participants. Females reported higher anxiety and depression than males. Single individuals had the lowest life satisfaction. Higher income levels are correlated with greater life satisfaction. Quarantine and vaccination were linked to higher life satisfaction and lower psychological distress. The regression showed that older age, being married and higher income were linked to lower depression and anxiety. Severity of infection and quarantine increased both depression and anxiety. Infection reduced life satisfaction, but severe cases showed a slight improvement in satisfaction, highlighting complex health and well-being relationships. Practical implications The findings reveal complex relationships, including unexpected resilience in severe COVID-19 cases. Originality/value This study offers insights into the impact of the COVID-19 pandemic on SWB and mental health in Hungary. By analyzing socioeconomic, demographic and pandemic-related factors in a large sample, it highlights complex relationships between quarantine, infection severity, vaccination and well-being. The findings contribute to understanding how these factors influence mental health, informing targeted interventions during health crises.

Clinical Profile and Outcomes of All Admitted COVID-19 Positive Patients with Primary Lung Cancer in a Tertiary Government COVID-19 Referral Center: A Retrospective Cohort Study

Background. COVID-19 infection poses a continuing challenge especially to those already with prior lung disease. To analyze such patients’ profile is essential in today’s health care management. Objective. The study aimed to compare the outcomes of COVID-19 confirmed patients with and without primary lung cancer in terms of hospital stay, recovery, and mortality. Methods. The study employed a retrospective cohort design. Chart review of all adult COVID-19 patients in Philippine General Hospital from January 2021 to June 2021 was done. A matched cohort study was conducted between COVID-19 patients with and without primary lung cancer. Results. Among the 953 COVID-19 patients, there were 14 patients with primary lung cancer. In terms of length of hospital stay, patients with primary lung cancer had shorter days from 1.32 to 15.1 days compared to 2.28 to 18.36 days in patients without primary lung cancer (p-value 0.271). Furthermore, they had 64% recovery rate compared to 78% in those without primary lung cancer (p-value 0.118). In terms of overall mortality rate, primary lung cancer patients had 36% rate as compared to 22% in the non-lung cancer group (p-value 0.119). Diabetes mellitus, mild to severe COVID, Remdesivir, and antibiotic use were associated with longer hospital stay while oxygen support via nasal cannula and invasive ventilation led to shorter hospital stay. Age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via face mask, high flow nasal cannula, invasive ventilation, antibiotic use, hemoperfusion and nebulization showed a decrease chance of recovery while on contrary, Remdesivir showed an increase chance of recovery. An increase mortality rate was seen among age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via facemask, high flow nasal cannula, invasive ventilation, antibiotics, hemoperfusion, and nebulization, in contrast to a decrease in Remdesivir therapy. Conclusions. Among all admitted COVID-19 patients, primary lung cancer patients were associated with shorter hospital stay (8.21+6.89days), lower rate of recovery (64%), and higher mortality rate (36%) as compared to those without primary lung cancer. However, based on the computed p-values for each outcome, these differences are not statistically significant.

A New Laboratory Tool for COVID-19 Severity Prediction, CENIL Score

A New Laboratory Tool for COVID-19 Severity Prediction, CENIL Score

Impact of SARS-CoV-2 infection on respiratory and gut microbiome stability: a metagenomic investigation in long-term-hospitalized COVID-19 patients.

During the coronavirus disease 2019 (COVID-19) pandemic, the exploration of microecology has been essential for elucidating the intricacies of infection mechanisms and the recovery of afflicted individuals. To decipher the interplay of microorganisms between the intestinal and respiratory tracts, we collected sputum and throat swabs and feces from COVID-19 patients and explored the mutual migration among intestinal and respiratory microorganisms. Using next-generation sequencing (NGS) technology, we investigated intestinal and respiratory microorganism intermigration in two patients with severe COVID-19 during their hospitalization. Notably, we observed an expedited recovery of microecological equilibrium in one patient harboring Mycobacterium avium. Comparative analyses between 32 healthy controls and 110 COVID-19 patients with different disease severities revealed alterations in predominant microorganisms inhabiting the respiratory and intestinal tracts of COVID-19 patients. Among the alterations, intestinal Bacteroides vulgatus (BV) was identified as a noteworthy microorganism that exhibited marked enrichment in patients with severe COVID-19. BV, when highly abundant, may inhibit the transitional growth of Escherichia coli/Enterococcus, indirectly prevent the overgrowth of salivary streptococci, and maintain lung/intestinal microecology stability. In summary, this study elucidates the bidirectional microbial intermigration between the intestinal and respiratory tracts in COVID-19 patients. These findings are expected to provide new ideas for the treatment and management of COVID-19, underscoring the essential role of microecology in infectious diseases. Nevertheless, a systematic study of the roles of BV in recovery from infection is required to gain a deeper understanding of the mechanisms of microbial migration.