COVID-19 in Unvaccinated patients with inherited metabolic disorders: A single center experience

Patients with certain inherited metabolic disorders (IMD) are at high risk for metabolic decompensation with exposure to infections. The COVID-19 pandemic has been particularly challenging for health care providers dealing with IMD patients, in view of its unpredictable consequences in these patients. There is limited data in literature on evaluating the impact and the outcome of COVID-19 infection in these patients. This cross-sectional retrospective study on a large cohort of unvaccinated IMD patients, reviewed the incidence of COVID-19 infection, disease manifestation and outcome during the pandemic between November 2019 and July 2021. In this cohort of 1058 patients, 11.7% (n = 124) were infected with COVID-19. Their median age was 16 years (age range 2–42); 57% (n = 71) were males. Post-exposure positive test was noted in 78% (n = 97) patients, while 19% (n = 24) had symptomatic diagnosis and three patients tested positive during pre-hospital visits screening. Most patients, 68.5% (n = 85) had mild COVID-19 related symptoms such as fever, cough, headache and diarrhea while 13.7% (n = 17) patients had no symptoms. Of twenty-two patients (17.7%) who required hospitalization, 16 were adults with various intoxication and energy metabolism disorders, who developed IMD related complications such as metabolic acidosis, hyperammonemia, acute pancreatitis, hypoglycemia, rhabdomyolysis and thrombosis. Ten patients needed intensive care management. The cohort death rate was 2.4% (3 patients).Overall, the clinical course of COVID-19 infection in these IMD patients was relatively mild except for patients with intoxication and energy metabolism disorders who had high risk of developing acute metabolic decompensation with severe complications.     

Impact of HLA polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in patients with renal replacement therapy

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection could present in a clinical spectrum of varying severity. Human leukocyte antigen (HLA) is a crucial component of the viral antigen presentation pathway and immune response to the virus. Therefore, we aimed to assess the impact of HLA allele polymorphisms on the susceptibility to SARS-CoV-2 infection and related mortality in Turkish kidney transplant recipients and wait listed patients, along with clinical characteristics of the patients. We analysed data from 401 patients with clinical characteristics according to presence (n = 114, COVID+) or absence of SARS-CoV-2 infection (n = 287, COVID-) who had previously been HLA typed to support transplantation. The incidence of coronavirus disease-19 (COVID-19) was 28 %, and the mortality rate was 19 % in our wait listed/ transplanted patients. Multivariate logistic regression analysis showed that a significant HLA association between HLA- B*49 (OR = 2.57, 95 % CI, 1.13–5.82; p = 0.02) and HLA- DRB1*14 (OR = 2.48, 95 % CI, 1.18–5.20; p = 0.01) with SARS-CoV-2 infection. Besides, in COVID + patients, HLA-C*03 was correlated to mortality (OR = 8.31, 95 % CI, 1.26–54.82; P = 0.03). The new finding from our analysis suggests that HLA polymorphisms could be associated with the occurrence of SARS-CoV-2 infection and COVID-19 mortality in Turkish patients with renal replacement therapy. This study may provide new information for the clinician to identify and manage sub-populations at risk in the setting of the current COVID-19 pandemic.     

National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: lessons from the first wave

ObjectivesThe impact of bacterial/fungal infections on the morbidity and mortality of persons with coronavirus disease 2019 (COVID-19) remains unclear. We have investigated the incidence and impact of key bacterial/fungal infections in persons with COVID-19 in England.MethodsWe extracted laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1st January 2020 to 2nd June 2020) and blood and lower-respiratory specimens positive for 24 genera/species of clinical relevance (1st January 2020 to 30th June 2020) from Public Health England's national laboratory surveillance system. We defined coinfection and secondary infection as a culture-positive key organism isolated within 1 day or 2–27 days, respectively, of the SARS-CoV-2-positive date. We described the incidence and timing of bacterial/fungal infections and compared characteristics of COVID-19 patients with and without bacterial/fungal infection.Results1% of persons with COVID-19 (2279/223413) in England had coinfection/secondary infection, of which >65% were bloodstream infections. The most common causative organisms were Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Cases with coinfection/secondary infections were older than those without (median 70 years (IQR 58–81) versus 55 years (IQR 38–77)), and a higher percentage of cases with secondary infection were of Black or Asian ethnicity than cases without (6.7% versus 4.1%, and 9.9% versus 8.2%, respectively, p < 0.001). Age-sex-adjusted case fatality rates were higher in COVID-19 cases with a coinfection (23.0% (95%CI 18.8–27.6%)) or secondary infection (26.5% (95%CI 14.5–39.4%)) than in those without (7.6% (95%CI 7.5–7.7%)) (p < 0.005).ConclusionsCoinfection/secondary bacterial/fungal infections were rare in non-hospitalized and hospitalized persons with COVID-19, varied by ethnicity and age, and were associated with higher mortality. However, the inclusion of non-hospitalized persons with asymptomatic/mild COVID-19 likely underestimated the rate of secondary bacterial/fungal infections. This should inform diagnostic testing and antibiotic prescribing strategy.     

Asthma in patients with suspected and diagnosed coronavirus disease 2019

BackgroundPatients with asthma are comparatively susceptible to respiratory viral infections and more likely to develop severe symptoms than people without asthma. During the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to adequately evaluate the characteristics and outcomes of the population with asthma in the population tested for and diagnosed as having COVID-19.ObjectiveTo perform a study to assess the impact of asthma on COVID-19 diagnosis, presenting symptoms, disease severity, and cytokine profiles.MethodsThis was an analysis of a prospectively collected cohort of patients suspected of having COVID-19 who presented for COVID-19 testing at a tertiary medical center in Missouri between March 2020 and September 2020. We classified and analyzed patients according to their pre-existing asthma diagnosis and subsequent COVID-19 testing results.ResultsPatients suspected of having COVID-19 (N = 435) were enrolled in this study. The proportions of patients testing positive for COVID-19 were 69.2% and 81.9% in the groups with asthma and without asthma, respectively. The frequencies of relevant symptoms were similar between the groups with asthma with positive and negative COVID-19 test results. In the population diagnosed as having COVID-19 (n = 343), asthma was not associated with several indicators of COVID-19 severity, including hospitalization, admission to an intensive care unit, mechanical ventilation, death due to COVID-19, and in-hospital mortality after multivariate adjustment. Patients with COVID-19 with asthma exhibited significantly lower levels of plasma interleukin-8 than patients without asthma (adjusted P = .02).ConclusionThe population with asthma is facing a challenge in preliminary COVID-19 evaluation owing to an overlap in the symptoms of COVID-19 and asthma. However, asthma does not increase the risk of COVID-19 severity if infected.     

Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM—a prospective,randomized, single-centre,open-label study

ObjectivesSevere COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage.MethodsPatients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission.ResultsClinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7–12) in the TCZ group and 12 days (interquartile range, 9–15) in the control group (p = 0.014).DiscussionIn patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.     

The role of the HLA allelic repertoire on the clinical severity of COVID-19 in Canadians,living in the Saskatchewan province

AimsThe HLA system has been implicated as an underlying determinant for modulating the immune response to SARS-CoV-2. In this study, we aimed to determine the association of patients’ HLA genetic profiles with the disease severity of COVID-19 infection.MethodsProspective study was conducted on COVID-19 patients (n = 40) admitted to hospitals in Saskatoon, Canada, between March and December 2020. Next-generation sequencing was performed on the patient samples to obtain high-resolution HLA typing profiles. The statistical association between HLA allelic frequency and disease severity was examined. The disease severity was categorized based on the length of hospital stay and intensive care needs or demise during the hospital stay.ResultsHLA allelic frequencies of the high and low-severity cohorts were normalized against corresponding background allelic frequencies. In the high-severity cohort, A*02:06 (11.8-fold), B*51:01 (2.4-fold), B*15:01(3.1-fold), C*01:02 (3.3-fold), DRB1*08:02 (31.2-fold), DQ*06:09 (11-fold), and DPB1*04:02(4-fold) were significantly overrepresented (p < 0.05) making these deleterious alleles. In the low-severity cohort, A*24:02 (2.8-fold), B*35:01 (2.8-fold), DRB1*04:07 (5.3-fold), and DRB1*08:11 (22-fold) were found to be significantly overrepresented (p < 0.05) making these protective alleles. These above alleles interact with NK cell antiviral activity via the killer immunoglobulin-like receptors (KIR). The high-severity cohort had a higher predilection for HLA alleles associated with KIR subgroups; Bw4-80I (1.1-fold), and C1 (1.6-fold) which promotes NK cell inhibition, while the low-severity cohort had a higher predilection for Bw4-80T (1.6-fold), and C2 (1.6-fold) which promote NK cell activation.ConclusionIn this study, the HLA allelic repository with the distribution of deleterious and protective alleles was found to correlate with the severity of the clinical course in COVID-19. Moreover, the interaction of specific HLA alleles with the KIR-associated subfamily modulates the NK cell-mediated surveillance of SARS-CoV-2. Both deleterious HLA alleles and inhibitory KIR appear prominently in the severe COVID-19 group focusing on the importance of NK cells in the convalescence of COVID-19.     

The differential immune response in mild versus fatal SARS-CoV2 infection

This study compared the immune response in mild versus fatal SARS-CoV2 infection. Forty nasopharyngeal swabs with either productive mild infection (n = 20) or negative for SARS-CoV2 (n = 20) were tested along with ten lung sections from people who died of COVID-19 which contained abundant SARS-CoV2 and ten controls. There was a 25-fold increase in the CD3+T cell numbers in the viral positive nasopharyngeal swabs compared to the controls (p < 0.001) and no change in the CD3+T cell count in the fatal COVID-19 lungs versus the controls. CD11b + and CD206+ macrophage counts were significantly higher in the mild versus fatal disease (p = 0.002). In situ analysis for SARS-CoV2 RNA found ten COVID-19 lung sections that had no/rare detectable virus and also lacked the microangiopathy typical of the viral positive sections. These viral negative lung tissues when compared to the viral positive lung samples showed a highly significant increase in CD3+ and CD8 T cells (p < 0.001), equivalent numbers of CD163+ cells, and significantly less PDL1, CD11b and CD206+ cells (p = 0.002). It is concluded that mild SARS-CoV2 infection is marked by a much stronger CD3/CD8 T cell, CD11b, and CD206 macrophage response than the fatal lung disease where viral RNA is abundant.     

HLA repertoire of 115 UAE nationals infected with SARS-CoV-2

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies.     

Association between SARS-CoV-2 infection and de novo HLA donor specific antibody production in lung transplant recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients. Respiratory viral infections may be associated with de-novo HLA donor-specific antibody production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in lung transplant recipients include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo HLA donor specific antibody production in lung transplant recipients. We performed a retrospective chart review of 24 consecutive lung transplant recipients diagnosed with COVID-19 to investigate this concern. We observed no significant differences in the CPRA or MFI levels of HLA class I and II antibodies pre- COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 11/24 (45.8 %) LTR (p = 0.98 and p = 0.63 respectively). HLA class I and II DSA were detected in 5/24 LTR pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.89). De-novo HLA class I and II DSA were detected in 1/24 (4.2 %) LTR at one month post-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.54). Our results suggest that there was no significant association between SARS-CoV-2 infection and immunomodulation on pre-existing or de novo HLA donor specific antibodies.     

Obesity,diabetes, hypertension and severe outcomes among inpatients with coronavirus disease 2019: a nationwide study

ObjectivesInitial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death.MethodsAll French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account.ResultsA total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9–2.1 and aOR 1.5, 95% CI 1.4–1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0–2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8–3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5–18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1–1.2) and diabetes (aOR 1.2, 95% CI 1.1–1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8–2.0), diabetes (aOR 1.4, 95% CI 1.3–1.4) and hypertension (aOR 1.7, 95% CI 1.6–1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3–3.7), diabetes (aOR 2.0, 95% CI 1.8–2.1) and hypertension (aOR 2.5, 95% CI 2.4–2.6).ConclusionsAmong 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.     

Evaluation of the relationship between serum levels of zinc,vitamin B12, vitamin D,and clinical outcomes in patients with COVID-19

Due to the known anti-inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored the association between serum levels of these micronutrients in coronavirus disease 2019 (COVID-19) patients at the time of admission and the clinical outcomes. This study was carried out on 293 patients with COVID-19, who were hospitalized at Imam Hassan hospital (Bojnourd, Iran). We collected demographic data, clinical characteristics, values of serum biochemical parameters in the first week of admission, and clinical outcomes from electronic medical records. We also measured serum levels of zinc, 25(OH)D, and vitamin B12 within 3 days of admission. Of the 293 hospitalized, the median age was 53 years, and 147 (50.17%) were female. Thirty-seven patients (12.62%) were admitted to the intensive care unit (ICU), and forty-two (14.32%) died. We found that the serum levels of zinc, vitamin B12, and 25(OH)D were lower in patients who died than those who were admitted to ICU or non-ICU and survived; however, these differences were not statistically significant for vitamin B12 and 25(OH)D (p > 0.05). The serum concentrations of zinc, vitamin B12, and 25(OH)D at the time of admission did not affect the length of hospital stay in patients with COVID-19. In general, it seems that serum levels of 25(OH)D, vitamin B12, and especially zinc at the time of admission can affect clinical outcomes in COVID-19 patients.     

HLA-G 14-bp insertion/deletion polymorphism and risk of coronavirus disease 2019 (COVID-19) among Iraqi patients

Human leukocyte antigen (HLA)-G molecules are proposed to influence susceptibility to coronavirus disease 2019 (COVID-19). A case-control study was conducted on 209 patients with COVID-19 and198 controls to assess soluble HLA-G (sHLA-G) levels and HLA-G 14-bp insertion [Ins]/deletion [Del] polymorphism. Results revealed that median levels of sHLA-G were significantly higher in serum of COVID-19 patients than in controls (17.92 [interquartile range: 14.86–21.15] vs. 13.42 [9.95–17.38] ng/mL; probability <0.001). sHLA-G levels showed no significant differences between patients with moderate, severe or critical disease. Del allele was significantly associated with the risk of COVID-19 (odds ratio = 1.89; 95% confidence interval = 1.44–2.48; corrected probability = 0.001), while a higher risk was associated with Del/Del genotype (odds ratio = 2.39; 95% confidence interval = 1.25–4.58; corrected probability = 0.048). Allele and genotype frequencies of HLA-G 14-bp Ins/Del polymorphism stratified by gender or disease severity showed no significant differences in each stratum. Further, there was no significant impact of genotypes on sHLA-G levels. In conclusion, sHLA-G levels were up-regulated in COVID-19 patients regardless of disease severity. Further, it is suggested that HLA-G 14-bp Ins/Del polymorphism is associated with COVID-19 risk.     

ABO blood group system is associated with COVID-19 mortality: An epidemiological investigation in the Indian population

BackgroundNovel coronavirus disease-19 (COVID-19) has spread worldwide, and to date presence of the virus has been recorded in 215 countries contributing 0.43 million of death. The role of blood groups in susceptibility/resistance to various infectious diseases has been reported. However, the association of blood groups with susceptibility to COVID-19 infections or related death are limited. In the present report, we performed an epidemiological investigation in the Indian population to decipher the importance of blood groups concerning susceptibility or mortality in COVID-19 infection.Materials and methodsData on COVID-19 infection and mortality was obtained from the website of the Government of India. Prevalence of ABO blood groups in different states and union territories of India were searched using different databases such as PubMed and Google Scholar. Relevant articles were downloaded, and data were extracted. Spearman's rank coefficient analysis was employed to study the correlation between blood group frequencies and COVID-19 infection or mortality rate.ResultsA significant inverse correlation was observed between the frequency of O blood group and the COVID-19 mortality rate (Spearman r = −0.36, P = 0.03), indicating a possible protective role of O blood group against COVID-19 related death. In contrast, the prevalence of blood group B was positively correlated with COVID-19 death/million (Spearman r = 0.67, P < 0.0001), suggesting B blood type as a deleterious factor in COVID-19 infection.ConclusionsABO blood group system is associated with poor prognosis of COVID-19 infection. Blood group O may protects, and subjects with blood type B could be susceptible to COVID-19 mortality. However, further studies on COVID-19 infected patients in different population are required to validate our findings.     

A hospital cluster of COVID-19 associated with a SARS-CoV-2 superspreading event

Background/purposeSuperspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE.MethodsWe performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied.ResultsPatient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (R_t) was 0.9 (8/9).ConclusionThe host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (R_t, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.     

COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28–1.18), 1.09 (95% CI = 0.27–4.47), and 0.67 (95% CI = 0.32–1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38–0.74) and death (OR: 0.13; 95% CI = 0.13–0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.     

More than loss of taste and smell: burning watering eyes in coronavirus disease 2019

ObjectivesTo evaluate ocular symptoms in European non-hospitalized patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and to investigate associations with the demographic data as well as nasal and general physical symptoms.MethodsIn this prospective, observational study, 108 non-hospitalized patients with PCR-confirmed SARS-CoV-2 infection not requiring intensive care were asked about disease-associated ocular symptoms, demographic data, as well as general physical and nasal symptoms using a standardized questionnaire. Total ocular symptom score (TOSS) was evaluated during and, retrospectively, before development of coronavirus disease 2019 (COVID-19). Associations between TOSS and demographic data as well as general and nasal symptoms were evaluated.ResultsSeventy-five of the 108 COVID-19 patients (69.4%) had at least one ocular symptom during COVID-19. The most common symptoms included burning sensations in 39 (36.1%), epiphora in 37 (34.3%) and redness in 28 (25.9%), compatible with conjunctivitis. These symptoms occurred 1.96 ± 3.17 days after the beginning of COVID-19 and were mild. TOSS was significantly higher during COVID-19 (1.27 ± 1.85) than before the infection (0.33 ± 1.04; p < 0.001). There were no significant associations between TOSS and gender (β coefficient –0.108; p 0.302), age (–0.024; p 0.816), rhinorrhoea (–0.127; p 0.353), nasal itching (–0.026; p 0.803), sneezing (0.099; p 0.470), nasal congestion (–0.012; p 0.930), cough (–0.079; p 0.450), headache (0.102; p 0.325), sore throat (0.208; p 0.052), or fever (0.094; p 0.361).ConclusionsOcular involvement in European non-hospitalized individuals with COVID-19 seems to be highly underestimated. Overall, these ocular symptoms, including burning sensations, epiphora and redness, seem to be mild and to not need treatment.     

HLA-DRB1*04 may predict the severity of disease in a group of Iranian COVID-19 patients

Human leukocyte antigen (HLA) genes with extreme diversity can make a contribution for individual variations to the immune response against SARS-COV-2 infection. This study aimed to explore the distributions of HLA class II alleles frequencies and their relations with disease severity in a group of Iranian COVID-19 patients. This prospective and case-control study was conducted on 144 COVID-19 patients including 46 cases with moderate form, 54 cases with severe and 44 cases with critical disease. HLA-DRB1 and -DQB1 allele families were determined by PCR-SSP method and compared between three groups of the patients and in comparison to 153 ethnic-matched healthy controls. The patients group showed lower frequencies of HLA-DRB1*15 (OR = 0.57, P = 0.06), DRB1*15 ~ DQB1*05 haplotype (P = 0.04) and DRB1*15/DRB1*04 genotype (P = 0.04) in compare with healthy controls. Moderate COVID-19 patients had higher frequencies of HLA-DRB1*04 (P = 0.03), HLA-DRB1*10 (P = 0.05) and DRB1*04/DRB1*11 genotype (P = 0.01). Also, a higher significantly frequency of HLA-DRB1*03 allele group was observed in the critical patients versus controls (P = 0.01). Multiple logistic regression analysis revealed that the presence of DRB1*04 allele group was negatively associated with development of severe and critical disease (OR: 0.289, P = 0.005). Our results indicate a possible contribution of some HLA class II alleles in disease severity and clinical features of COVID-19 disease.     

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial

ObjectivesThe potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients.MethodsA multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were ≥50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion.ResultsAfter the enrolment of 421 patients and the transfusion in 416 patients, recruitment was discontinued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59–1.22). The OR was 0.58 (95% CI, 0.33–1.02) for patients with ≤5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28–1.34). No difference was found in viral RNA excretion or in the duration of symptoms.ConclusionsIn patients with early COVID-19, CP therapy did not improve the 5-point disease severity score.     

The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection

Pre-existing Alzheimer's disease is a risk factor for severe/fatal COVID-19 and infection by SARS-CoV2 virus has been associated with an increased incidence of un-masked Alzheimer's disease. The molecular basis whereby SARS-CoV2 may amplify Alzheimer's disease is not well understood. This study analyzed the molecular changes in autopsy brain tissues from people with pre-existing dementia who died of COVID-19 (n = 5) which was compared to equivalent tissues of people who died of COVID-19 with no history of dementia (n = 8), Alzheimer's disease pre-COVID-19 (n = 10) and aged matched controls (n = 10) in a blinded fashion. Immunohistochemistry analyses for hyperphosphorylated tau protein, α-synuclein, and β-amyloid-42 confirmed the diagnoses of Alzheimer's disease (n = 4), and Lewy body dementia (n = 1) in the COVID-19 group. The brain tissues from patients who died of COVID-19 with no history of dementia showed a diffuse microangiopathy marked by endocytosis of spike subunit S1 and S2 in primarily CD31+ endothelia with strong co-localization with ACE2, Caspase-3, IL6, TNFα, and Complement component 6 that was not associated with SARS-CoV2 RNA. Microglial activation marked by increased TMEM119 and MCP1 protein expression closely paralleled the endocytosed spike protein. The COVID-19 tissues from people with no pre-existing dementia showed, compared to controls, 5-10× fold increases in expression of neuronal NOS and NMDAR2 as well as a marked decrease in the expression of proteins whose loss is associated with worsening Alzheimer's disease: MFSD2a, SHIP1, BCL6, BCL10, and BACH1. In COVID-19 tissues from people with dementia the widespread spike-induced microencephalitis with the concomitant microglial activation co-existed in the same areas where neurons had hyperphosphorylated tau protein suggesting that the already dysfunctional neurons were additionally stressed by the SARS-CoV2 induced microangiopathy. ACE2+ human brain endothelial cells treated with high dose (but not vaccine equivalent low dose) spike S1 protein demonstrated each of the molecular changes noted in the in vivo COVID-19 and COVID-19/Alzheimer's disease brain tissues. It is concluded that fatal COVID-19 induces a diffuse microencephalitis and microglial activation in the brain due to endocytosis of circulating viral spike protein that amplifies pre-existing dementia in at least two ways: 1) modulates the expression of proteins that may worsen Alzheimer's disease and 2) stresses the already dysfunctional neurons by causing an acute proinflammatory/hypercoagulable/hypoxic microenvironment in areas with abundant hyperphosphorylated tau protein and/or βA-42.