Severe COVID-19 Disease Research Articles

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.

Alteration of the Gut–Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study

Background: The gut–lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators. Aim: We conducted a pilot study to understand alterations in the gut–lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease. Methods: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut–lung axis at baseline and throughout probiotic intervention. Results: Compared to mCOV patients, sCOV patients showed lower microbial richness, which was significantly improved by probiotic intervention. A reorganization of Ruminococcaceae and Lachnospiraceae taxa was observed in sCOV patients but remained unaffected by the intervention. Serum metabolome showed a dysregulation of lipoproteins in accordance with higher BMI and comorbidities in sCOV patients. HDL and LDL fractions/components were temporarily decreased in the probiotic group. Stool metabolome was altered at baseline in sCOV patients and an increase in L-DOPA after 3 months and butyrate after 6 months of intervention could be observed. Probiotics partially improved reduced quality of life and modulated altered immune responses in sCOV patients. Increased intestinal permeability at baseline remained unaffected. Conclusion: The study provides evidence of long-term alterations of the gut–lung axis after severe COVID-19 infection and suggests that probiotics can modulate the biomarkers of the gut–lung axis.

Association between Hematological Parameters and Severity of COVID-19 disease

Background This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID-19 disease and their use in predicting severity of COVID-19 disease. Methods and Material This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center. Statistical analysis used The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 disease, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve. Results The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity. Conclusions The hematological parameters mentioned, can be used for predicting severe COVID-19 disease at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being < 1105 cells/cubic millimeter and > 10.434 respectively.

Variations in COVID-19 vaccine hesitancy over time: a serial cross-sectional study in five West African countries

ObjectivesThis study aims to identify the factors influencing vaccine hesitancy, willingness and its variation over time in order to inform more responsive strategies for increasing vaccination uptake. The specific objectives...

Comparative effectiveness of monovalent XBB.1.5 containing covid-19 mRNA vaccines in Denmark, Finland, and Sweden: target trial emulation based on registry data

ObjectiveTo estimate the effectiveness of vaccination with a monovalent covid-19 mRNA vaccine containing the omicron XBB.1.5 subvariant against severe covid-19 disease in Denmark, Finland, and Sweden.DesignTarget trial emulation based on registry data.SettingDenmark, Finland, and Sweden, 1 October 2023 to 21 April 2024.ParticipantsSource population of 3 898 264 individuals eligible for vaccination with the XBB.1.5 containing covid-19 mRNA vaccine at the start of the study on 1 October 2023. Study cohort comprised 1 876 282 recipients of an XBB.1.5 containing vaccine during the study period matched with 1 876 282 non-recipients. Individuals were aged ≥65 years (mean age 75.4 years, standard deviation 7.4 years) and had received at least four doses of a previous covid-19 vaccine.Main outcome measuresCumulative incidences of hospital admissions and deaths related to covid-19 in a follow-up period of 24 weeks after immunisation (defined as one week after vaccination) in recipients of an XBB.1.5 containing covid-19 mRNA vaccine and matched non-recipients. Cumulative incidences were used to calculate comparative vaccine effectiveness (1−risk ratio) and risk differences.ResultsThe associated comparative vaccine effectiveness was 57.9% (95% confidence interval (CI) 49.9% to 65.8%) against hospital admission for covid-19 (1085 v2635 events) and 75.2% (70.6% to 79.9%) against deaths related to covid-19 disease (348 v1458 events) after 24 weeks of follow-up. This result corresponded to 154.7 (95% CI 78.3 to 231.0) hospital admissions for covid-19 and 120.3 (110.5 to 130.2) deaths prevented per 100 000 individuals who were vaccinated with an XBB.1.5 containing vaccine. The associated comparative vaccine effectiveness was similar irrespective of sex, age group (65-74v≥75 years), number of doses of previous covid-19 vaccines, subgroup of co-administered seasonal influenza vaccines, and period of when either the omicron XBB or BA.2.86 sublineage was predominant. Although the observed reduction in risk was highest during the first weeks after vaccination, comparative vaccine effectiveness was well maintained after 24 weeks of follow-up.ConclusionsIn this study, in adults aged ≥65 years, vaccination with a monovalent XBB.1.5 containing covid-19 mRNA vaccine was associated with reduced rates of hospital admissions for covid-19 and deaths related to covid-19, during the autumn and winter of 2023-24 in Denmark, Finland, and Sweden.

Mortality related to different circulatory diseases: a multiple causes of death analysis, 2008-2022

Abstract Background Mortality from circulatory diseases significantly increased in 2020 compared to pre-pandemic years in many countries. However, data were mostly limited to the underlying cause of death and to the first phases of the pandemic. Analyses of any mention of a disease in death certificates (multiple causes of death approach, MCOD) are more robust to changes in coding rules/practices and to the role of COVID-19 as a competing cause of death. Methods Mortality records were extracted from 2008 to 2022 among residents of the Veneto Region (Northeastern Italy, 4.9 million population). Based on MCOD, age-standardized mortality rates (2013 European standard) were computed for ischemic heart diseases (IHD), cerebrovascular diseases (CVD), atrial fibrillation (AF), and hypertensive diseases (HD). The annual percent change (APC) was estimated through the pre-pandemic period (2008-2019), and change in rates during pandemic years were computed compared to 2019. Results Before the pandemic, rates were steeply declining for IHD (APC -5.1%; 95%CI -5.5, -4.6) and CVD (-4.0%; -4.4, -3.5); mortality related to HD reduced at a slower pace (-1.9%; -2.3, -1.4), whereas AF-related mortality was increasing (+1.0%; 0.1, 1.8). During the first year of the pandemic, the growth in mortality compared to 2019 was +26% for HD, +18% for AF, +13% for CVD and +12% for IHD. In 2021-2022, rates for CVD and IHD returned to pre-pandemic levels; rates for HD reduced with respect to 2020 but remained above the baseline; AF-related mortality was still increasing. Conclusions The pandemic differentially impacted mortality associated to different circulatory diseases, depending on pre-existing long-term trends (increasing for AF) and on susceptibility to severe COVID-19 disease (higher for HD). Continuous surveillance based on MCOD is warranted to properly assess changes in mortality associated to specific circulatory diseases after the end of the pandemic. Key messages • Multiple causes of death analyses are warranted to assess how the pandemic affected pre-existing long term trends in cause-specific mortality. • Mortality related to different circulatory diseases increased in 2020, but pre-pandemic trends, the extent of the increase in 2020, and further changes observed in 2021-2022 largely diverged.

Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein < 27 mg/L. We randomized 294 patients: 96 to LPVr, 100 to LPVr + TLM, 98 to LPVr + ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr + TLM arm (p = 0.69) and 43% in the LPVr + ATV arm (p = 0.68). The median time from baseline to resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr + TLM arm and 2 in the LPVr + ATV arm and 4 patients died. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.Trial registration: NCT04466241, registered on 10/07/2020

Nursing Interventions Related to the Need for Oxygenation in Severe COVID-19 Disease in Hospitalized Adults: A Retrospective Study.

To describe the nursing interventions related to the need for oxygenation in hospitalized adults with severe COVID-19 disease in the Intensive Care Unit. This was an observational, retrospective and descriptive study in a population of 2205 patients with a convenience sample of n = 430 and based on the North American Nursing Diagnosis Association (NANDA), the Nursing Interventions Classification (NIC) and the Nursing Outcomes Classification (NOC). The analysis was performed with a non-parametric test to determine the association between the nursing interventions and the need for oxygenation. The findings are aimed at improving nursing interventions with statistical associations as follow: oxygen therapy (p < 0.000), airway suctioning (p < 0.000), airway management (p = 0.029), invasive mechanical ventilation (p < 0.000) and non-invasive mechanical ventilation (p = 0.022). NOC taxonomy expected outcomes in ventilation, 34% (146), alteration in gas exchange, 33.7% (145), and respiratory status, 558.9% (253), were severely compromised. The nursing interventions to maintain the respiratory status are focused on airway care and oxygen therapy in order to increase the oxygen saturation level and decrease the severity of the need for oxygenation.

Oral Health Related Factors Predicting Severe COVID-19 Disease in Elderly Swedes.

To analyse different background factors that may serve as predictors for acquiring symptoms of severe COVID-19 disease. A postal questionnaire was sent to the total population of individuals born between 1942 (80 years, n = 6299) and 1932 (90 years, n = 1904) living in the Örebro and Östergötland counties, Sweden, in 2017 and repeated in 2022. Tentative predictive factors for self-reported severe COVID-19 disease were based on the responses from the 2017 questionnaire related to general and oral health and prior to the outbreak of the COVID-19 pandemic. Response rate to the main questionnaire in 2022 was 66% (5375/8203), and 577 reported having been sick with COVID-19 out of which 359 agreed to answer a separate questionnaire on COVID-19. This questionnaire was returned by 278/359 of the participants corresponding to a response rate of 77%. Information gleaned from the 2017 pre-COVID-19 survey revealed a relatively large number of associations between severity of subsequently self-reported COVID-19 disease and several diverse tentative related factors found in unadjusted regression analyses. Based on statistically significant correlations in the adjusted regression analysis, significant predictive factors (based on self-reports from 2017) for contracting severe COVID-19 were in decreasing order of odds ratios (OR): reported removable partial or complete denture usage (OR 6.2, CI 2.2-17.2); reported periodontal problems in the past year (OR 3.4, CI 1.1-10.4); and reported daytime dry mouth (OR 2.5, CI 1.2-5.2). Removable dentures, periodontal problems and daytime dry mouth were predictors for developing symptoms of severe COVID-19 disease.

Complete Blood Count in Children With COVID-19: A Predictor of Disease Severity.

Blood count abnormalities are frequent in patients with severe COVID-19 disease and there is still a lack of information in pediatric complete blood count (CBC) results. Thus, this study aims to correlate the CBC in the emergency room of children with COVID-19 between 0 and 10 years old and the clinical severity of the disease. A retrospective cohort study was performed in children with COVID-19 who collected at the emergency room CBC, C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), lymphocyte to neutrophil ratio (LNR), lymphocyte to monocyte ratio (LMR), monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR). In total, demographic data from 93 children with median age of 19 months (0.3-126), 60.2% males, were included. The main changes in the CBC were atypical lymphocytes (51.6%) and eosinopenia (49.5%). From 69 hospitalized children, 21 were considered severe. There was no association between age, gender, and CRP value with clinical severity. The presence of underlying disease was five times higher (odds ratio [OR] = 5.08) in patients who required hospitalization and a higher NLR value was 54% (OR = 1.54) more likely to occur. Eosinopenia was three times more frequent in inpatients with disease severity criteria (OR = 3.05). In conclusion, children younger than 10 years of age with COVID-19 have changes in the CBC collected in the emergency room, mainly atypical lymphocytes and eosinopenia. The presence of a comorbidity or a higher NLR increases the chance of hospitalization. In addition, eosinopenia was a predictor of severity in inpatient children due to COVID-19.

Association of COVID-19 risk factors with systemic fungal infections in hospitalized patients.

A new category of systemic co-infections that emerged with the COVID-19 pandemic is known as COVID-19-associated (CA) fungal infections, which include pulmonary aspergillosis (CAPA), candidiasis (CAC), and mucormycosis (CAM). We aimed to study the association between patient characteristics of hospitalized COVID-19 patients, COVID-19 comorbidities, and COVID-19 therapies with secondary non-superficial fungal infections. We performed descriptive and regression analyses of data from 4,999 hospitalized COVID-19 patients from the University of Kentucky Healthcare (UKHC) system. The patients with secondary systemic fungal infections had a 6-fold higher risk of death than those without such infections. Generally, the risk factors for severe COVID-19 (age, obesity, cardiovascular disease, diabetes, and lack of COVID-19 vaccination) were strong predictors of a secondary fungal infection. However, several characteristics had much higher risks, suggesting that a causative link may be at play: ICU admission, mechanical ventilation, length of hospital stay, and steroid use. In sum, this study found that the known risk factors for severe COVID-19 disease, age, diabetes, cardiovascular disease, obesity, ventilation, and high steroid doses were all predictors of a secondary fungal infection. Steroid therapy may need to be modified to account for a risk or a presence of a fungal infection in vulnerable patients.

Children with sickle cell disease: are they protected from serious COVID-19?

COVID-19, the pandemic that hit the world in 2020, resulted in millions of deaths, with the elderly and adults succumbing to the disease more often than children. However, the presence of underlying morbidities increased the risk of death. Sickle cell disease (SCD) was previously classified as a major risk factor for severe COVID-19 disease. However, presently, there are only a limited number of studies that identify the clinical course of children with SCD and COVID-19. We conducted a retrospective observational study on children with SCD admitted due to COVID-19 at three different institutions in Saudi Arabia between March 2020 and March 2022. We studied the demographic and clinical characteristics of patients admitted to the hospital. Seventy-six patients with SCD had PCR-confirmed SARS-CoV-2 during the study period; 50.0% of our patient population were children (6-12 years old). Gender was evenly distributed, with 53.9% girls and 46.1% boys. Symptoms more commonly related to the COVID-19 infection included fever, cough, malaise, and vomiting. Chest x-ray findings revealed mild and non-specific symptoms only in approximately one-third (28) of the included children. The most common symptoms associated with SCD were vaso-occlusive crisis (47.4%) and abdominal pain (11.8%). The overall general appearance of most of the patients was reassuring. The median length of hospital stay was 4.2 ± 2.7 days. The mean white blood cell count was 11.4 ± 5.2 × 109/L, and the mean hemoglobin level was 8.3 ± 1.5 g/dl. Despite the fact that higher levels of mean D-dimer, lactate dehydrogenase, and ferritin were reported in these patients, the clinical outcome was not affected. All recruited patients received hydroxyurea as maintenance therapy. The outcome of our study was reassuring, with no significant morbidity or mortality observed among the recruited patients. Despite SCD being a chronic disease with known specific complications, there has been a claim that COVID-19 infection adds further risk. The results of this study suggest that the overall outcome of COVID-19 was favorable, with no reported mortality. Further research is needed to understand the factors that contributed to this favorable outcome. In children with SCD, it is still questionable whether hydroxyurea is one of the protective factors against severe COVID-19. Validation through large-scale research is recommended.

Hemophagocytosis of the Hilar Pulmonary Lymph Nodes Is a More Sensitive Indicator of the Severity of COVID-19 Disease than Bone Marrow Hemophagocytosis.

In systemic hyper-inflammation, as in severe COVID-19 disease, there are pronounced disorders of the hematological and lymphatic systems with prognostically relevant hemophagocytosis of the bone marrow. The current work aimed to address the importance of hemophagocytosis in the lymph nodes of patients with severe COVID-19 disease. From 28 patients who died of severe COVID-19 infection, samples of the vertebral bone marrow and lymph nodes from the cervical, hilar, para-aortic, mesenteric and inguinal locations were morphologically and immunohistologically (CD163, CD68, CD61, CD71, CD3, CD20, CD138) examined for the possible presence of hemophagocytosis. In the single-center study at the University Hospital Jena, a total of 191 hemophagocytes were found in the bone marrow and a total of 780 hemophagocytes in the lymph nodes in a standardized area of 21,924 mm2 per tissue sample. With 370 hemophagocytes, hilar lymph nodes were most frequently affected (370/780; 47.44%; 95%-CI: [43.94, 50.95]), followed by cervical lymph nodes (206/780; 26.41%; 95%-CI: [23.41, 29.59]), para-aortic lymph nodes (125/780; 16.03%; 95%-CI: [13.58, 18.73]) and inguinal/mesenteric lymph nodes (79/780; 10.13%; 95%-CI: [8.155, 12.4]). Based on the standard area (21,924 mm2), the difference in the number of hemophagocytes in the bone marrow and in the hilar lymph nodes was statistically significant (p < 0.05), while this did not apply to the lymph nodes from the other locations. In fatal COVID-19 disease, hemophagocytosis is particularly found in the hilar lymph nodes and is therefore a better indicator of the severity of the disease than hemophagocytosis in the bone marrow. The findings provide some evidence for the concept of compartmentalized human host responses to life-threatening infections.

Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series.

The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.

COVID-19-Associated Hospitalizations and Maternal Vaccination Among Infants Aged

Infants aged <6 months are at increased risk for severe COVID-19 disease but are not yet eligible for COVID-19 vaccination; these children depend upon transplacental transfer of maternal antibody, either from vaccination or infection, for protection. COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) data were analyzed to estimate COVID-19-associated hospitalization rates and identify demographic and clinical characteristics and maternal vaccination status of infants aged <6 months hospitalized with laboratory-confirmed COVID-19. During October 2022-April 2024, COVID-NET identified 1,470 COVID-19-associated hospitalizations among infants aged <6 months. COVID-19-associated hospitalization rates among young infants were higher than rates among any other age group, except adults aged ≥75 years, and are comparable to rates among adults aged 65-74 years. The percentage of hospitalized infants whose mothers had been vaccinated during pregnancy was 18% during October 2022-September 2023 and decreased to <5% during October 2023-April 2024. Severe outcomes among infants hospitalized with COVID-19 occurred frequently: excluding newborns hospitalized at birth, approximately one in five young infants hospitalized with COVID-19 required admission to an intensive care unit, nearly one in 20 required mechanical ventilation, and nine infants died during their COVID-19-associated hospitalization. To help protect pregnant persons and infants too young to be vaccinated, prevention for these groups should focus on ensuring that pregnant persons receive recommended COVID-19 vaccines.

COVID-19 vaccination in people living with HIV: current data and perspectives.

There is no correlation between HIV per se and other risk factors for severe COVID-19 disease. Pivotal studies have shown that vaccination is one of the effective ways to prevent severe COVID-19 illness in the general population. Studies on people living with HIV (PLWH) are scarce. The majority of these studies with mRNA (BNT126b2 and mRNA-1273) and adenovirus vector (Ad26.COV2.2 and ChAdOx1) vaccines with a low number of patients included shows that PLWH on antiretroviral treatment and with CD4 count > 200/mm³ has a robust immune response. These vaccines are thus effective in preventing severe infection caused by severe acute respiratory syndrome coronavirus 2 in PLWH. However, PLWH with a CD4 count of < 200/mm³ and uncontrolled viral load (VL) seems to have a lower immune response. COVID-19 vaccines are safe in PLWH; adverse effects are mild or moderate, and their incidence is similar to non-HIV people (NHP). The CD4 count decreased significantly and transiently, and the VL rebounded insignificantly in a few patients. A complete vaccination including a third dose is, therefore, recommended. A booster dose with an mRNA vaccine is recommended in PLWH with an advanced stage of their disease.

Clinical practice guideline supported administration of monoclonal antibody therapy for high-risk patients with COVID-19: Experience of a quaternary care centre

Background: Immunocompromised patients remain at risk of progression to severe COVID-19 disease. Methods: We describe clinical COVID-19-related outcomes after administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) following institutional clinical practice guidelines (CPGs) in 205 high-risk patients between November 2021 and April 2022 at a Canadian quaternary care centre. Results: Median patient age was 59 years; 102 (50%) were female. Eighty-two (40%) were transplant recipients, 47 (23%) patients had hematologic malignancies, 25 (12%) had solid organ malignancies, and 51 (25%) had another indication. Forty-eight (23%) had received fewer than two doses of anti-SARS-CoV-2 vaccines. The majority (80%) had mild disease at presentation with 14% moderate and 6% severe. Median time from symptom onset to mAb administration was 3 days (IQR 2.0-5.5 days). Of those who received mAb as outpatients, 90 (93%) had favourable clinical outcomes (no COVID-19-related hospitalizations or death within 3 months). Of those who received mAb as inpatients, 93 (86%) had favourable outcomes (discharged without COVID-19-related re-admission or death), 4% were re-admitted, and 10% died. In logistic regression analysis, only disease severity at time of mAb administration was associated with unfavourable outcomes. Fewer than two vaccine doses was not associated with unfavourable outcomes, suggesting potential benefit among the under-vaccinated. There was a significant difference in adherence to CPGs between administration of mAb in outpatients versus inpatients (adherent for 85% versus 58%, p&lt;0.001), where non-adherence occurred in cases of severe disease. Conclusion: CPG-supported mAb administration for management of COVID-19 in high-risk patients was associated with favourable clinical outcomes and may be a useful model to guide future therapies.

SARS-CoV-2 replicates in the placenta after maternal infection during pregnancy.

Pregnant women are at increased risk for severe SARS-CoV-2 infection and adverse neonatal outcome, primarily preterm birth and stillbirth. Our study aimed to investigate to which extent SARS-CoV-2 affects placental tissue and if viral replication within the placenta is evident, thus if there is a correlation between placental damage and adverse pregnancy outcome such as stillbirth. We prospectively collected placentas from 61 SARS-CoV-2 infected pregnant women and 10 controls. Histopathological, immunohistochemical, and in situ hybridization studies were performed on all placentas with antibodies for SARS-CoV-2 proteins, ACE2, various immune cells, and inflammatory markers or probes for SARS-CoV-2 genes and an antisense strand. The measured scores of SARS-CoV-2 glycoprotein, nucleocapsid, and antisense strand indicating replication correlated with both the severity of maternal symptoms and presence of stillbirth. Specifically, 15/61 placentas exhibited replication, while the three cases with stillbirth had high or maximal replication scores. ACE2-H-score was significantly higher in COVID-19 patients, while the expression of various immune cells did not differ statistically. In multivariate analysis, presence of maternal comorbidities correlated with presence of severe COVID-19 infection. We report evidence of active in vivo SARS-CoV-2 replication in the placenta after maternal infection in pregnancy in a case-control setting in a large population. Intensity of placental viral replication as well as viral levels were higher in women with severe or critical COVID-19 disease, supporting the rationale that severity of maternal SARS-CoV-2 infection could correlate with the severity of placentitis. Replication was maximal in cases of stillbirth, which suggests direct placental involvement in the pathophysiology of this dramatic outcome. Continuing to advocate for preventive measures against COVID-19 during pregnancy, including (re)vaccination, as well as appropriately counseling women with diagnosed infection, are of utter importance.

Association between Hematological Parameters and Severity of COVID-19 disease.

This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID-19 disease and their use in predicting severity of COVID-19 disease. This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center. The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 disease, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve. The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity. The hematological parameters mentioned, can be used for predicting severe COVID-19 disease at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being < 1105 cells/cubic millimeter and > 10.434 respectively.

A real-world study of BBIBP-CorV vaccine effectiveness in a Sri Lanka rural province

ObjectiveReal-world studies assessing the effectiveness of the BBIBP-CorV vaccine in low and middle-income countries are limited. We evaluated the BBIBP-CorV vaccine's effectiveness in reducing COVID-19 symptomatic disease, hospitalisation, severe disease, and mortality during the third wave of the pandemic in Sri Lanka. MethodsWe conducted a test-negative case-control study in North Central Province from May 2021 to February 2022. Evidence of vaccination was obtained from the national registry. The PCR-positive patients were cases, while negative individuals were controls. Adjusted vaccine effectiveness (aVE) was computed for fully, partially, and non-vaccinated groups in reducing symptomatic disease, hospitalisation, severe disease, and mortality. ResultsOur study involved 3305 cases and 3418 controls. The overall aVE for preventing PCR-positive infection in fully vaccinated was 30·8 % (95 % CI:17·9–41·6). In fully vaccinated over 60 years, the overall aVE was 72·3 % (95 % CI: 49·7–84·8). Full vaccination with BBIBP-CorV is effective in reducing hospitalisation, severe COVID-19 disease, and death, with aVE rates of 70·3 % (95 % CI: 57·9–79·0), 88·9 % (95 % CI: 81·8–93·2), and 92·3 % (95 % CI: 84·8–96·1) respectively. ConclusionIndividuals who have received two doses of the BBIBP-CorV vaccine are protected against hospitalisation, severe COVID-19 disease, and death. Duration of protection against hospitalisation, severe COVID-19, and fatal COVID-19 sustained at least 121 days, with no sign of waning during that time.