Severe Coronavirus Disease 2019 Disease Research Articles

SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized patients.

Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitzii and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.IMPORTANCEOutcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes.

Effectiveness of laboratory tests in tracking severely COVID-19 infections

AIM: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that causes COVID-19 (Coronavirus Disease 2019), and poses serious difficulties in terms of healthcare systems and global public health. With the large number of publications on COVID-19, clinicians need a synthesis of evidence to provide guidance when dealing with patients with COVID-19. Emerging studies reveal the existence of numerous demographic, clinical, immunological, biochemical and radiographic data that may be useful for clinicians to predict the severity and mortality of COVID-19. The aim is of this study; To determine laboratory parameters that can predict the course and severity of COVID-19 disease in patients with diagnosed solely SARS-CoV 2 PCR test positivity results and independently of the clinic status of selected patients and based on laboratory findings. MATERIALS AND METHODS: This study is a retrospective cross-sectional study conducted at Karacabey State Hospital between January and April 2022. Among the patients who applied to the COVID-19 outpatient clinic, 469 patients (261 females, 208 males) over the age of 18 and positive for SARS-CoV-2 RT-PCR were included in the study. The patients were divided into groups as outpatients, inpatients and patients in need of intensive care (intensive care unit, ICU). Demographic data (age, gender), COVID-19 RT-PCR results, and simultaneous laboratory parameters of the patients were scanned retrospectively. RESULTS: When CRP, urea, ferritin, LEU, NEU, MONO, RBC, HGB, HCT, MCV, NLR, PLR, CRP-NR, and SII index values were taken into consideration, a statistically significant difference was found between the groups. Creatinine, ALT, AST, LDH, troponin I, mass CK-MB, D dimer, LYM, EOS, PLT, ELR, and PNR values were not significantly different between the groups. CONCLUSIONS: Advantages of this study; Comparing the changes in the patient's other laboratory findings based on a single positive PCR test result and finding meaningful rates in terms of serious covid risk. The disadvantage of this study is that it is a study independent of the patient's clinic and disease stage. CRP, urea, ferritin, and indexes such as NLR, PLR, CRP-NR, and SII index values can be used to predict the severity of the disease.

Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity

BackgroundIn 2019, coronavirus disease 2019 (COVID-19) emerged in China, spreading globally with significant impacts in Japan, including the Delta and Omicron variants. The research identified risk factors such as age, chronic diseases, and lifestyle choices, emphasizing the need for further study on the association between underlying health conditions, treatments, and COVID-19 severity in Japan.MethodsThis study used a nationwide medical database to analyze the association between COVID-19 underlying conditions and pharmacological interventions to identify risk factors for disease severity. We examined the Japanese COVID-19 dataset from Medical Data Vision, selecting patients diagnosed with COVID-19 between January 2020 and December 2022. Logistic regression was used to calculate the odds ratios (ORs) for intensive care unit treatment- or ventilator use-related risk factors.ResultsAmong 650,317 patients (mean age: 52.1 ± 20.9 years; male individuals: 324,127; female individuals: 326,190), factors that significantly increased the severe disease risk (OR [95% confidence interval]) included age > 65 years (1.31 [1.27–1.36]), hypertension (1.34 [1.28–1.41]), cardiovascular disease (1.74 [1.67–1.81]), and use of beta-blockers (2.09 [2.00–2.17]), calcium blockers (1.97 [1.89–2.06]), angiotensin-converting enzyme inhibitors (1.41 [1.33–1.49]), low-dose aspirin (1.38 [1.32–1.45]), and insulin (7.14 [6.87–7.43]). Conversely, factors that reduced the severe disease risk included female sex and the use of sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists, and alpha-glucosidase inhibitors.ConclusionsPatients using cardiovascular medications faced a higher risk, whereas those receiving diabetes treatment had a lower risk. Appropriate pharmacotherapy and risk factor identification can aid in the prevention of severe COVID-19.

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not: A systematic review and meta-analysis.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease. To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients. A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs). Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76]. Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

Sulfated Bile Acids in Serum as Potential Biomarkers of Disease Severity and Mortality in COVID-19.

The fight against coronavirus disease 2019 (COVID-19) continues. Since the pandemic's onset, several biomarkers have been proposed to assess the diagnosis and prognosis of this disease. This research aimed to identify potential disease severity biomarkers in serum samples of patients with COVID-19 during the disease course. Data were collected using untargeted and targeted mass spectrometry methods. The results were interpreted by performing univariate and multivariate analyses. Important metabolite classes were identified by qualitative untargeted metabolomics in 15 serum samples from survivors of COVID-19. Quantitative targeted metabolomics on a larger patient cohort including 15 non-survivors confirmed serum 3-sulfate bile acids (i.e. GLCA-3S) were significantly increased in non-survivors compared to survivors during the early disease stage (p-value < 0.0001). Notably, it was associated with a higher risk of mortality (odds ratio of 26). A principal component analysis showed the ability to discriminate between survivors and non-survivors using the BA concentrations. Furthermore, increased BA-S is highly correlated with known parameters altered in severe clinical conditions.

Causal Inference of the Effect of Vaccination on COVID-19 Disease Severity and Need for Intensive Care Unit Admission Among Hospitalized Patients in an African Setting.

Background Coronavirus disease 2019 (COVID-19) is a novel, primarily respiratory, coronavirus that became a pandemic when it spread to over 210 countries and led to the death of over six million people. There is no definitive treatment for COVID-19, but vaccines have been developed that can help prevent severe illness and death. Studies have investigated the effect of vaccination on disease severity and outcome, and the findings indicate that vaccination is linked to a significant reduction in the risk of hospitalization, intensive care unit (ICU) admission, and disease mortality. However, there is a scarcity of evidence in Africa in general, and no similar study has been conducted in Ethiopia yet. Therefore, the study aimed to assess the effect of vaccination on COVID-19 disease severity and the need for ICU admission among hospitalized patients at a private specialty clinic in Ethiopia. Methods A retrospective cohort study was conducted among 126 patients with COVID-19, 41 vaccinated and 85 unvaccinated, who were hospitalized between September 2021 and May 2022. Data were summarized using frequency (percentage) and median (interquartile range (IQR)). To compare the characteristics of the two groups, Chi-square/Fisher's exact and Mann-Whitney U tests at p-values of ≤ 0.05 were used. To identify the effect of vaccination on COVID-19 disease severity, a marginal structural model (MSM) with an inverse probability weighting (IPW) approach using a robust Poisson regression model was fitted. Adjusted relative risk (ARR) and 95% confidence interval (CI) for ARR were used for interpreting the result. Results The cohort included groups that were comparable in terms of their sociodemographic and clinical characteristics. More than half of the participants were older than 60 years (n = 66, 52.4%), were males (n = 71, 56.3%), and had one or more comorbid illnesses (n = 66, 52.4%). At admission, 85 (67.5%) had severe disease, and 11 (8.7%) progressed after hospitalization and required ICU admission, of which three unvaccinated cases died. From the final model, vaccination was found to be associated with a 62% decreased risk of developing severe COVID-19 disease if infected, compared to not getting vaccinated (ARR = 0.38, 95% CI = 0.23-0.65, p < 0.0001). Conclusions The study's findings support previous reports that vaccinated people are less likely to develop severe COVID-19 disease if later infected with the virus, emphasizing the importance of continuing efforts to promote COVID-19 vaccination not only to safeguard individuals but also to confer community-level immunity.

Antihistamine and COVID-19 outcomes in outpatients.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Since then, researchers have been investigating the efficacy and side effects of its medication, up until now. From the viewpoint of Persian medicine, some medications such as antihistamines may cause retention of secretions and lead to exacerbation and spread of the disease in the body. There are studies with conflicting results regarding the effectiveness of antihistamines in COVID-19. Systematic reviews found a lack of data on beneficial effect of antihistamine-decongestant-analgesic combinations for the common cold and a limited short-term effect of antihistamines on severity of overall symptoms. This prospective cohort study was designed to investigate the relationship between the use of antihistamines and the severity of COVID-19 symptoms. Three hundred patients with a diagnosis of COVID-19 participated in the study in Shiraz, Iran from December 4, 2021 until January 24, 2022. The interviews were conducted via phone call by a single interviewer. Patients were followed weekly for 4 weeks. We collected information by using a data collection form, containing demographic information, underlying disease, COVID-19 symptoms, treatment methods, medications, and a list of antihistamines and herbs that might have been used. Generalized estimating equations were applied to assess the relationship between the severity of COVID-19 and the use of antihistamines, taking into account potential confounding factors such as time and herbal consumption. The difference in the severity of COVID-19 disease in antihistamine users compared to nonusers was not significant in 4 weeks despite the higher baseline severity in nonusers. The comparison of two groups of antihistamine users and nonusers showed that there was a significant difference (p = 0.001) regarding the use of herbal medicines.

Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and disease severity in adult patients: A prospective cohort study in a tertiary hospital, Indonesia.

Coronavirus disease 2019 (COVID-19) has led to a significant number of infections and deaths worldwide, yet its pathogenesis and severity remain incompletely understood. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), play crucial roles as receptors and molecules responsible for the virus's entry into host cells, initiating the infection process. Their polymorphisms have been extensively studied in relation to COVID-19 severity. The aim of this study was to examine the association of ACE2 (rs2074192) and TMPRSS2 (rs12329760) polymorphisms with COVID-19 outcome and severity. A prospective cohort study was conducted in 2022 at Haji Adam Malik Hospital, Medan, Indonesia. We randomly recruited hospitalized adult patients with COVID-19, confirmed by real-time polymerase chain reaction (RT-PCR). The baseline demographic data, disease severity, underlying disease, comorbidities, and COVID-19 vaccination status were collected. The single-nucleotide polymorphism (SNP) was assessed using TaqMan SNP genotyping assay, and the levels of TMPRSS2 and ACE2 proteins were measured using enzyme-linked immunosorbent assay (ELISA). A total of 151 COVID-19 patients were recruited and there were significant associations between age and severity with mortality outcomes. The age, kidney and lung diseases, and vaccination status were associated with severity levels. The results showed the CC genotype of ACE2 had the highest proportion, followed by TT and CT genotypes among patients, while CT was the most prevalent genotype, followed by CC and TT for TMPRSS2. This study did not find a significant association between ACE2 and TMPRSS2 genetic variants with disease severity and outcome but highlighted a specific association of TMPRSS2 SNP with mortality within the group. In addition, ACE2 concentration was significant different between mild-moderate and severe-critical COVID-19 groups (p=0.033).

COVID19 Vaccination Considerations for Pregnant Women: A Systematic Review.

Following the coronavirus disease 2019 (COVID-19) pandemic, pregnant women are at a higher risk of developing severe COVID-19 disease. This study investigated whether pregnant women should get vaccinated against COVID-19 or not. Pregnant women in comparison with non-pregnant women. This study was a systematic review that searched the PubMed, Embase, and Scopus databases using the keywords "COVID-19" OR "SARS-CoV-2" OR "Coronavirus Disease" OR "2019-nCoV" AND "pregnancy "OR "pregnant" AND "vaccine" OR "vaccination" from January 2020 to April 2022. Of the 37 selected studies, 15 (40.50%) declared positive views, 9 (24.30%) had inconclusive views, and 13 (35.20%) opposed vaccination due to a lack of adequate information. Despite the discrepancies among the studies, one-third of the studies suggested that pregnant women be enrolled in clinical trials to investigate the outcomes of the COVID-19 vaccination on maternal and fetal outcomes. However, the majority of the studies recommended maternal immunization against COVID-19.

Eighteen-Month Outcomes Among Pregnant and Nonpregnant Reproductive-Aged People Hospitalized for Coronavirus Disease 2019.

Physiologic and immunologic adaptations in pregnancy may increase the risk of adverse outcomes from respiratory viral infections. However, data are limited on longer-term outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy prior to widespread vaccine availability. Using electronic health record data, we retrospectively compared 6-, 12-, and 18-month outcomes including death and rehospitalization between pregnant and nonpregnant reproductive-aged individuals hospitalized for SARS-CoV-2 infection between 2020 and 2021 at 2 academic referral hospitals. There were 190 nonpregnant and 70 pregnant participants. Mean age was 31 years for pregnant and 34 years for nonpregnant participants. For pregnant patients, mean gestational age at coronavirus disease 2019 (COVID-19) diagnosis was 36 weeks, 54% delivered by cesarean, and 97% delivered a live birth. Compared to pregnant participants, nonpregnant participants had a higher prevalence of baseline comorbidities and a higher proportion received mechanical ventilation (84% vs 55%). Index hospitalization complications (31% vs 17%) and mortality (3% vs 0%) were more common in nonpregnant participants. Over 18 months following index hospitalization, 39 (21%) nonpregnant and 5 (7%) pregnant participants were readmitted, most for infection (28/44 [64%]). Most readmissions occurred within 6 months. There were no posthospitalization deaths in the pregnant group. Pregnant people with severe COVID-19 disease had a low rate of severe adverse outcomes after index hospitalization. The low readmission rate is reassuring that pregnant individuals may not be at higher risk for long-term severe adverse health outcomes after COVID-19 compared to the nonpregnant reproductive-aged population, possibly because any increased risk conferred by pregnancy resolves soon after delivery.

Outcomes of Obese Coronavirus 2019 Patients Treated with Extra Corporeal Membrane Oxygenation

Background: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is used as salvage therapy in severe cases of acute respiratory distress syndrome (ARDS) caused by the coronavirus disease 2019 (COVID-19). Obesity has been linked to worse disease severity and poor outcomes in COVID-19, but there is also a hypothesized obesity survival paradox whereby obese patients fare better in severe illness than their non-obese complement. The effect of obesity on ECMO outcomes in patients with COVID-19 is not well understood. Methods: We performed a retrospective analysis of all patients admitted to our institution who underwent VV ECMO cannulation for COVID-19 in the span of one year. These were separated by body mass index (BMI) with a cutoff of 35 kg/m2 (signifying class 2 obesity or higher) and compared with each other as well as a comparator group of patients with BMI &gt;35 kg/m2 who underwent VV ECMO cannulation for any cause between 2016 and 1 March 2021. Disease severity was categorized using established scoring systems including Apache-II, Charleson-Dayeo, and Murray. Primary endpoints were 30 day mortality, survival to decannulation, and survival to discharge. Results: The study groups were similar in all respects with the exception of BMI. Illness severity, as classified by Charleson-Dayeo, Apache II, and Murray scores not significantly different between groups. The primary outcomes (30-day mortality, survival to decannulation, and survival to discharge) were not significantly different between groups. There was a trend toward more delayed inititation of ECMO therapy in the obese group that was not statistically significant. There was also a trend toward shorter duration of ECMO therapy that did not reach the threshold for statistical significance. Conclusions: There was no significant difference in outcomes between obese and non-obese patients undergoing VV ECMO for COVID-19. Trends toward shorter duration of ECMO and shorter intensive care unit (ICU) and hospital length of stay could represent the “obesity survival paradox” that has been described. Given similar outcomes, obesity should not be a contraindication to ECMO therapy for COVID-19.

The association between non-communicable diseases and COVID-19 severity and mortality among infected hospitalized healthcare workers in 29 countries: a cohort study

Background Due to occupational exposure, healthcare workers (HCWs) have a higher risk of Coronavirus Disease 2019(COVID-19) infection than the general population. Non-communicable diseases (NCDs) may increase the risk of COVID-19-related morbidity and mortality among HCWs, potentially reducing the available health workforce. We examined the association between NCDs and COVID-19 disease severity and mortality among infected HCWs. Methods This cohort study used data from the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) database. HCWs hospitalized between January 2020 and January 2023 due to clinically suspected or laboratory-confirmed COVID-19 were eligible for inclusion. Variables collected included demographic data, comorbidities, and hospitalization outcomes. Descriptive statistics were reported using mean/standard deviation (SD), median/interquartile range (IQR), or frequencies and proportions. For each NCD, the relative risk of death, adjusted for age and sex, was calculated using log-binomial regression as well as the population-attributable fraction. Results There were 17,502 HCWs, 95.7% of whom had a confirmed COVID-19 diagnosis. The majority were female (66.5%) and the mean age (SD) was 49.8 (14.3) years. Roughly, half (51.42%) of HCWs had no comorbidities, 29.28% had one comorbidity, 14.68% had 2 comorbidities and &lt;5% had ≥3 comorbidities. The most common comorbidities were diabetes mellitus (49.40%) and cardiovascular disease (36.90%). Approximately one-fifth of the HCWs had severe COVID-19 (16.95%) and 10.68% of the HCWs with COVID-19 died. Being ≥45 years old, male gender, smoking, obesity, and certain NCDs increased the risk of COVID-19 severity and mortality. Obesity and diabetes mellitus were the leading risk factors in terms of the population-attributable risk for COVID-19 severity (6.89%) and mortality (36.00%) respectively. Conclusions Many HCWs with COVID-19 had one or more NCDs. Obesity and diabetes mellitus increased COVID-19 severity and mortality risk. Reducing the prevalence of obesity and diabetes mellitus would yield the biggest reduction in COVID-19-related morbidity and mortality among HCWs.

Effects of Viral Infections Like COVID-19 on Head and Neck Cancers: The Role of Neutrophil-Lymphocyte Counts and Ratios.

Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth. Various studies have shown a positive association between increasing neutrophil-to-lymphocyte ratio (NLR) and disease severity in COVID-19. Studies have also shown that high NLR is associated with poor survival outcomes in cancer patients. Our aim is to investigate whether an increased NLRis linked to rapid tumor progression in patients with HNSCCwho have also been affected by infections like COVID-19 in the pre-operative period. This was a retrospective analysis of patients of HNSCC who were scheduled for surgery and had contracted COVID-19 in their pre-operative period between April 2021 and May 2021.The study analyzed pre- and post-COVID NLR in relation to disease progression in HNSCC.Statistical analysis was presented as an interquartile range and numbered with the percentage. StatisticalPackage for the Social Sciences (IBMSPSSStatisticsforWindows,IBMCorp., Version 26.0, Armonk,NY) was utilized for the analysis. We evaluated 200 operable cases of which 38/200 (20%) patients with HNSCC were COVID-19 positive. Out of those COVID-19-positive patients, 27/38 (71%) patients got operated. Around, 11/38 (28.9%) patients were inoperable. And, 14/27 (53.8%) operated patients also had a change in treatment plan. The mean duration from the joint clinic treatment plan to the date of surgery was 25.18 days.Patients who had contracted COVID-19 and had a change in their treatment plan due to disease progression exhibited mean NLR values of 3.84 (pre-COVID) and 11.11 (post-COVID), with respective medians of 3.04 and 10.50. These differences showed a statistically significant p-value of 0.000. In contrast, patients who had no change in treatment plan displayed mean NLR values of 4.51 (pre-COVID) and 9.70 (post-COVID), with respective medians of 3.47 and 3.42, resulting in with a non-significant p-value of 0.082. This is a one-of-its-kind study that has evaluated the role of elevated NLR in patients with a COVID-19 virus infection and its relationship with the clinical progression of the disease. The findings suggest that elevated NLR in patients with HNSCC, along with concurrent SARS-CoV2 infection, may contribute to accelerated disease progression with an increase in tumor burden and nodal metastasis.

Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes.

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus's ability to infect vascular cells.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. Clinical Trials Registry-India (CTRI/2020/08/027000).

COVID-19 in pregnancy: A cross-sectional study on clinical features, disease severity, and health outcome.

Assessing the impact of coronavirus disease 2019 (COVID-19) reveals unique challenges for pregnant women, who experience distinct clinical manifestations and health outcomes compared to their non-pregnant counterparts. We aimed to evaluate the clinical features, disease severity, and health outcomes of COVID-19 in pregnant women and compare them to those of non pregnant women. In this population-based study, we included all women diagnosed with COVID-19 across the province of Tehran during the first two years of the epidemic. Descriptive statistics, the chi-squared test, and the logistic regression model were applied. Overall, 79,338 non-pregnant women and 3249 pregnant women diagnosed with COVID-19 were included. Pregnant women were most commonly in the age group of 25 - 34 years (54%, n = 1758), while the age group of 34-44 had the highest representation among non-pregnant women (56%, n = 44,492). After accounting for age and comorbidities, pregnancy was associated with an increased risk of requiring intensive care (odds ratio [OR] 1.38, confidence interval [CI] 1.223 - 1.564). However, the probability of dying due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was lower in pregnant women compared to non-pregnant women (OR 0.55, CI 0.394-0.793). Cough (41%) and fever (30%) were the most frequent clinical presentations in pregnant women, whereas cough (57%) and muscle ache (38%) were the most common symptoms in non-pregnant women. Furthermore, diarrhea (P < 0.001) and skin lesions (P < 0.001) were reported more frequently by pregnant patients than non-pregnant patients. A significant prevalence of diabetes (P < 0.001), hypertension (P < 0.001), cancers (P < 0.001), and chronic hematological diseases (P < 0.001) was observed in pregnant patients. In conclusion, COVID-19-infected pregnant women exhibit different clinical manifestations and a more severe clinical course but have better health outcomes compared to their non-pregnant counterparts.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

SARS-CoV-2 superinfection in CD14+ monocytes with latent human cytomegalovirus (HCMV) promotes inflammatory cascade

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has posed significant challenges to global health. While much attention has been directed towards understanding the primary mechanisms of SARS-CoV-2 infection, emerging evidence suggests co-infections or superinfections with other viruses may contribute to increased morbidity and mortality, particularly in severe cases of COVID-19. Among viruses that have been reported in patients with SARS-CoV-2, seropositivity for Human cytomegalovirus (HCMV) is associated with increased COVID-19 risk and hospitalization. HCMV is a ubiquitous beta-herpesvirus with a seroprevalence of 60–90 % worldwide and one of the leading causes of mortality in immunocompromised individuals. The primary sites of latency for HCMV include CD14+ monocytes and CD34+ hematopoietic cells. In this study, we sought to investigate SARS-CoV-2 infection of CD14+ monocytes latently infected with HCMV. We demonstrate that CD14+ cells are susceptible and permissive to SARS-CoV-2 infection and detect subgenomic transcripts indicative of replication. To further investigate the molecular changes triggered by SARS-CoV-2 infection in HCMV-latent CD14+ monocytes, we conducted RNA sequencing coupled with bioinformatic differential gene analysis. The results revealed significant differences in cytokine-cytokine receptor interactions and inflammatory pathways in cells superinfected with replication-competent SARS-CoV-2 compared to the heat-inactivated and mock controls. Notably, there was a significant upregulation in transcripts associated with pro-inflammatory response factors and a decrease in anti-inflammatory factors. Taken together, these findings provide a basis for the heightened inflammatory response, offering potential avenues for targeted therapeutic interventions among HCMV-infected severe cases of COVID-19. SummaryCOVID-19 patients infected with secondary viruses have been associated with a higher prevalence of severe symptoms. Individuals seropositive for human cytomegalovirus (HCMV) infection are at an increased risk for severe COVID-19 disease and hospitalization. HCMV reactivation has been reported in severe COVID-19 cases with respiratory failure and could be the result of co-infection with SARS-CoV-2 and HCMV. In a cell culture model of superinfection, HCMV has previously been shown to increase infection of SARS-CoV-2 of epithelial cells by upregulating the human angiotensin-converting enzyme-2 (ACE2) receptor. In this study, we utilize CD14+ monocytes, a major cell type that harbors latent HCMV, to investigate co-infection of SARS-CoV-2 and HCMV. This study is a first step toward understanding the mechanism that may facilitate increased COVID-19 disease severity in patients infected with SARS-CoV-2 and HCMV.

Comparative analysis of various laboratory biomarkers based on the severity of COVID-19 in a tertiary care hospital in South India

COVID-19 (Corona Virus Disease 2019) was a life-changing pandemic with impact on social, environmental, health, and economic issues. Various inflammatory and hematological biomarkers studied individually or in combination in the literature have shown significant results with regard to COVID-19 pathology, severity, and prognosis. Yet the question of interest is how covid-19 inflammatory cascade impacts the interlink between the biomarkers during different stages. This study aims to retrospectively analyse ferritin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, blood urea nitrogen (BUN), creatinine, D-dimer, Lactate Dehydrogenase (LDH), C Reactive Protein (CRP) and Interleukin-6 (IL-6) levels between two groups based on COVID-19 severity. A retrospective cross-sectional study was conducted with laboratory data of COVID-19 patients admitted at Sri Ramachandra Medical College Hospital, India. The sample size was 104 [Group1: severe disease, n=52; Group-2: mild disease, n=52]. After normality testing, data were compared between the two groups followed by correlation analysis between the variables. A p&lt;0.05 was considered statistically significant. On comparison, Group 2 (severe COVID-19 disease) showed significant difference in the levels of all the biomarkers (p&lt;0.005) except Creatinine (p&lt;0.128) when compared with Group 1 (mild COVID-19 disease). Significant correlation was obtained between all biomarkers (p&lt;0.005) except creatinine. The correlation analysis primarily explains the inflammatory cascade involved in disease. Ferritin appears to have a standalone effect on disease severity, progression, organ dysfunction. This understanding can be used to provide better and more timely care.

Narrative Review Explaining the Role of HLA-A, -B, and -C Molecules in COVID-19 Disease in and around Africa.

The coronavirus disease 2019 (COVID-19) has left a devasting effect on various regions globally. Africa has exceptionally high rates of other infectious diseases, such as tuberculosis (TB), human immunodeficiency virus (HIV), and malaria, and was not impacted by COVID-19 to the extent of other continents Globally, COVID-19 has caused approximately 7 million deaths and 700 million infections thus far. COVID-19 disease severity and susceptibility vary among individuals and populations, which could be attributed to various factors, including the viral strain, host genetics, environment, lifespan, and co-existing conditions. Host genetics play a substantial part in COVID-19 disease severity among individuals. Human leukocyte antigen (HLA) was previously been shown to be very important across host immune responses against viruses. HLA has been a widely studied gene region for various disease associations that have been identified. HLA proteins present peptides to the cytotoxic lymphocytes, which causes an immune response to kill infected cells. The HLA molecule serves as the central region for infectious disease association; therefore, we expect HLA disease association with COVID-19. Therefore, in this narrative review, we look at the HLA gene region, particularly, HLA class I, to understand its role in COVID-19 disease.