Mechanistic insight into the protective and pathogenic immune-responses against SARS-CoV-2.

COVID-19 is a severe respiratory illness that has emerged as a devasting health problem worldwide. The disease outcome is heterogeneous, which is most likely dependent on the immunity of an individual. Asymptomatic and mildly/moderate symptomatic (non-severe) patients likely develop an effective early immune response and clear the virus. However, severe symptoms dominate due to a failure in the generation of an effective and specific early immune response against SARS-CoV-2. Moreover, a late surge in pathogenic inflammation involves dysregulated innate and adaptive immune responses leading to local and systemic tissue damage and the emergence of severe disease symptoms. In this review, we describe the potential mechanisms of protective and pathogenic immune responses in "mild/moderate" and "severe" symptomatic SARS-CoV-2 infected people, respectively, and discuss the immune components that are currently targeted for therapeutic intervention.

Biochemical and hematological factors associated with COVID-19 severity among Gabonese patients: A retrospective cohort study.

The COVID-19 disease presents a large range of clinical manifestations and includes asymptomatic, mild, and severe cases. The level of severity is related to parameters associated with immunity, genetics, and biochemistry. Africa shows one of the lowest COVID-19 fatality rates but very few data on the biochemical markers of COVID-19 in patients and the factors associated with disease severity are available for the continent. In Gabon, the COVID-19 fatality rate is only 0.63% but almost no data on biomarkers in COVID-19 patients have been published. Both the number of COVID-19 cases and the mortality rate reported in Africa in general, and in Gabon in particular, are lower than in non-African countries. As such, understanding the factors associated with disease severity in Gabonese patients is a crucial step to better understand the disease in the African context and prepare for future COVID-19 waves and other epidemics of emerging diseases. Here, we compared biochemical and hematological markers among 753 Gabonese COVID-19 patients with asymptomatic (184/753), mild/moderate (420/753), and severe/critical (149/753) forms of the disease using an Analysis of Variance (ANOVA) or a Kruskal-Wallis (KW) test. We modeled these parameters together with comorbidities, age, and sex to predict factors associated with disease severity by using a "binomial generalized linear model" utilizing the "package" stats of R software version 4.0.2. Our results showed that almost all the biochemical and hematological parameters (except creatinine, phosphorus, D-dimers, platelets, and monocytes) varied according to disease severity. However, age and the dysfunction of organs like the kidney, liver, and lung together with the decrease of electrolytes (chloride, potassium, and sodium) are the best predictors of disease severity in Gabonese patients.

Post-COVID-19 conditions in Ecuadorian patients: an observational study.

BACKGROUND: Post-COVID-19 disease is not yet clearly described, presenting significant clinical variability across populations and patients. This paper compares post-COVID symptoms in three patient groups with mild, moderate, and severe infections in Ecuadorian outpatients. METHODS: An epidemiological, observational, descriptive, and cross-sectional study was performed, and carried out in Quito, Ecuador. 1,366 non-hospitalized participants between 12 to 85 years, diagnosed with COVID-19 infection by molecular RT-PCR were included in the study. Demographic characteristics, including age groups, sex, ethnic group, work type, residence type, comorbidities, diagnosis, symptoms, and treatment were studied. FINDINGS: 1,366 outpatient Ecuadorian patients were analysed with SARS-CoV2 infection confirmed with a PCR+ test. The mean age was 39 (± 10) years, distributed by age groups ranging between 12 and 85 years; 81.41% were between 18 and 54 years. 50.29% were men, and 49.71% were women. INTERPRETATION: 64.3% of patients had symptoms between 4 to 6 weeks after infection, 21.1% showed ongoing symptoms between 6 to 12 weeks, and 14.6% had symptoms for more than 12 weeks. The most common symptom was fatigue in 67.3% of patients, followed by headache in 45.2%, body pain in 42.3%, and sleep disorders (insomnia, sleep apnoea, restless leg syndrome) in 36.5%. 69.3% of patients showed mild infection, 21.7% moderate, and 9.0% severe infection. On average, patients' daily life activities showed a 6.8% mean degree of impact following infection. A sedentary lifestyle (walking less than 30 minutes a day) was the most critical risk factor (40.3%), followed by being a health worker (11.87%). Patients aged ≥55 years with HTN, CKD, smoking, and sedentary lifestyle were 4.39, 1.92, 9.19, 4.07, and 2.42 times more likely to have a severe infection level. At least 30% of patients do not feel recovered from COVID-19 infection. FUNDING: The author declares that the financial resources for the preparation of this research come from their self-management.

Lymphopenia: A useful predictor of COVID-19 disease severity and mortality.

OBJECTIVE: To detect association of lymphopenia with disease severity and mortality. METHODS: Total 874 COVID RT-PCR positive patients admitted to KRL Hospital Islamabad from April 2020 to August 2020 were included in this cross-sectional study. Lymphopenia was defined as <1100 cells/micro-L. WHO categories for disease severity were used. Demographic profile, absolute lymphocyte counts and co-morbidities were recorded. Pearson's Chi Square test was used to see association between lymphopenia and disease severity as well as disease outcome. Regression analysis was used to see whether lymphopenia would predict disease severity. Comparison of means of absolute lymphocyte count in different disease categories was done by ANOVA. Tukey's test range was then used to find the means different from each other. P-value ≤ 0.05 was considered statistically significant. RESULTS: The mean age of patients was 40 ± 12.3 years. Majority patients (73.9%) were asymptomatic. Lymphopenia was present in 6.9% of total patients. Significant association was found between lymphopenia and disease severity as well as lymphopenia and mortality (< 0.001). Lymphopenia was found to be a predictor of disease severity using regression analysis (< 0.001). Comparison of mean absolute lymphocyte count was significant among disease severity categories (< 0.001). On post-hoc analysis, difference in absolute lymphocyte count was significant moving from asymptomatic to mild and then moderate disease category. However no significant difference was seen in absolute lymphocyte count between moderate and severe categories. CONCLUSION: Results are compatible with worldwide studies and lymphopenia is valid as a marker of disease severity and mortality.

Implementation and outcomes of monoclonal antibody infusion for COVID-19 in an inner-city safety net hospital: A South-Bronx experience.

BACKGROUND: Monoclonal antibody therapy (MAT) is recommended in mild to moderate Coronavirus disease 2019 (COVID-19) patients who are at risk of progressing to severe disease. Due to limited data on its outcomes and the logistic challenges in administering the drug, MAT has not been widely used in the United States (US) despite of emergency use authorization (EUA) approval by the Food and Drug Administration (FDA). AIM: We aim to study the outcomes of MAT in patients predominantly from ethnic minority groups and the challenges we experienced in implementing the infusion therapy protocol in an inner-city safety-net-hospital in the South Bronx. METHODS AND RESULTS: We conducted a retrospective observational study of 49 patients who were offered MAT as per EUA protocol of FDA. Patient who met the criteria for MAT and received therapy were included in treatment group (n = 38) and the remaining (n = 11) who declined treatment were included in the control group. A majority of patients (76%) in the study group reported symptomatic improvement, the day after infusion. There was statistically significant reduction in COVID-19 related hospitalizations (7.8 vs 54.5%, P = < 0.001) mortality (0 vs 18.1%, P value = 0.008) in the treatment group. CONCLUSION: MAT reduced both hospitalization and mortality in this predominantly Hispanic patient population with mild to moderate COVID-19 with high risk factors for disease progression.

[Potentially useful drugs in the treatment of COVID-19 in Primary Care]. / Fármacos potencialmente útiles en el tratamiento de la COVID-19 en Atención Primaria.

The consequences of the SARS-CoV-2 pandemic have exceeded any forecast made. Today we know that the level of severity of the infection in its initial stages will correspond to the evolution and the presence of sequelae in the future. There are no specific treatments that have shown sufficient evidence to allow their recommendation, especially in the mild-moderate stages of the disease. The anti-Covid vaccination is showing clear benefits, both in the prevention of the disease and in its evolution, with the consequent improvement in the numbers of those affected by the pandemic. The use of different drugs used in other indications has been proposed as possible beneficial treatments for COVID-19 that, if used, will be prescribed individually taking into account the characteristics and situation of the patient, the evolutionary phase of the disease as well as well as the limitations of the lack of evidence in its administration.

Independent Risk Factors for the Dynamic Development of COVID-19: A Retrospective Study.

OBJECTIVE: To identify the risk factors for predicting the dynamic progression of COVID-19. METHODS: A total of 2321 eligible patients were included in this study from February 4 to April 15, 2020. Two illness conditions, including mild/moderate (M/M) subtype to severe/critical (S/C) and S/C to fatality, were classified. Clinical message was collected and compared, respectively. Kaplan-Meier method, Cox regression model and risk score system were used to predict disease progression in S/C COVID-19. RESULTS: A total of 112 of 1761 patients with M/M subtype were progressors (P) and 1649 non-progressors (NP). Increasing disease progression associated with higher levels of neutrophils count (HR=1.958, 95% CI=1.253-3.059, P=0.003), CK (HR=2.203, 95% CI=1.048-4.632, P=0.037), LDH (HR=3.309, 95% CI=2.083-5.256, P<0.001) and CRP (HR=2.575, 95% CI=1.638-4.049, P<0.001), and lower level of lymphocytes count (HR=1.549, 95% CI=1.018-2.355, P=0.041), as well as total lesion volume ratio greater than ≥10% (HR=2.286, 95% CI=1.451-3.601, P<0.001) on admission. In progression to fatality, 56 of the 672 S/C cases died and 616 survived. Increasing fatality associated with lower level of lymphocytes count (HR:2.060, 95% CI:1.000-4.242, P=0.050), higher levels of BUN (HR:2.715, 95% CI:1.539-4.790, P<0.001), CK-MB (HR:3.412, 95% CI:1.760-6.616, P<0.001), LDH (HR:5.578, 95% CI:2.317-13.427, P<0.001), and PT (HR:3.619, 95% CI:2.102-6.231, P<0.001). Furthermore, high risk of neutrophils count, lymphocytes count, CK, LDH, CRP, and total lesion volume ratio was powerfully correlated with the incidence of progression to S/C in patients with NS COVID-19 and high odds of lymphocytes count, BUN, CK-MB, LDH, and PT were significantly associated with death in patients with S/C COVID-19. In addition, the progression and mortality rates increased with increasing risk scores. CONCLUSION: Elevated LDH level and lymphopenia were independent predictors for COVID-19 sustainable management in classifying non-severe patients who progressed to severe condition and identifying S/C patients who deteriorated to fatal outcomes as well. Total lesion volume ratio ≥10% may provide early predictive evidence with COVID-19 patients at high risk of developing into S/C to improve prognosis.

Prediction of the Rehabilitation Duration and Risk Management for Mild-Moderate COVID-19.

OBJECTIVES: More than 80% of coronavirus disease 2019 (COVID-19) cases are mild or moderate. In this study, a risk model was developed for predicting rehabilitation duration (the time from hospital admission to discharge) of the mild-moderate COVID-19 cases and was used to conduct refined risk management for different risk populations. METHODS: A total of 90 consecutive patients with mild-moderate COVID-19 were enrolled. Large-scale datasets were extracted from clinical practices. Through the multivariable linear regression analysis, the model was based on significant risk factors and was developed for predicting the rehabilitation duration of mild-moderate cases of COVID-19. To assess the local epidemic situation, risk management was conducted by weighing the risk of populations at different risk. RESULTS: Ten risk factors from 44 high-dimensional clinical datasets were significantly correlated to rehabilitation duration (P < 0.05). Among these factors, 5 risk predictors were incorporated into a risk model. Individual rehabilitation durations were effectively calculated. Weighing the local epidemic situation, threshold probability was classified for low risk, intermediate risk, and high risk. Using this classification, risk management was based on a treatment flowchart tailored for clinical decision-making. CONCLUSIONS: The proposed novel model is a useful tool for individualized risk management of mild-moderate COVID-19 cases, and it may readily facilitate dynamic clinical decision-making for different risk populations.

High prevalence of occult thrombosis in cases of mild/moderate COVID-19.

BACKGROUND AND PURPOSE: An increasing number of reports have observed thrombosis in severe cases of COVID-19. The aim of this study was to evaluate the incidence of thromboembolism in mild/moderate cases of COVID-19. All of the patients had normal coagulation tests and none had any overt thrombotic complications. Our findings indicate that it is important to screen the thrombotic status of cases with mild/moderate COVID-19. METHODS: Between 11 June and 8 July 2020, 23 patients with mild/moderate COVID-19 pneumonia consented to having computed tomography pulmonary angiography (CPTA) and computed tomography venography (CTV) scans of the lungs and extremity veins. Doppler ultrasound (DUS) was also performed in all patients for screening. The incidence, clinical manifestations, laboratory examinations, imaging features, and prognosis, of patients with venous thromboembolism (VTE) were analyzed and compared with those of patients with COVID-19 pneumonia without VTE. RESULTS: Nineteen patients (82.6%) had VTE, mainly distal limb thrombosis. Only one of the VTE patients was positive when screened by DUS; the other VTE patients were negative by DUS. All of the mild/moderate patients with VTE were screened by CTPA + CTV. Blood tests for inflammatory, coagulation, and biochemical, parameters were all within the normal range, except for WBC and LDH. CONCLUSIONS: When using CTV screening for DVT, we found that the incidence of thrombosis in patients with mild/moderate COVID-19 markedly increased to 82.6% (19/23). Screening for thrombosis is therefore important in patients with COVID-19. CTV is more sensitive than DUS for the detection of thrombosis. More research is now needed to evaluate the significance of thrombosis in COVID-19 pneumonia.

COVID-19 Surge Capacity Solutions: Our Experience of Converting a Concert Hall into a Temporary Hospital for Mild and Moderate COVID-19 Patients.

The 2019 coronavirus disease (COVID-19) pandemic has stressed the health care system in Italy as well as around the world, with hospitals implementing their surge capacity to increase the number of available beds for patients positive to the virus.At the end of March, the Piemonte (Northern Italy) Government decided to build a temporary rapid-assembly emergency hospital for the treatment of mild and moderate COVID-19 patients, converting an existing concert hall in the city of Turin. The decision was prompted not only by the urgent need of hospital beds, but also by a forward-looking approach for the months immediately after the emergency, when it will be essential for conventional hospitals to return to a normal configuration.This paper documents the temporary hospital project, describing the site, the layout and the equipment, the idea behind structural choices, and the staff involved. The aim of the work is to share the experience and to provide some practical recommendations to other professionals who are fighting the COVID-19 pandemic worldwide.

[Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients].

Objective To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Methods Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. Results There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43±16) years vs. (52±16) years; t=2.10, P=0.040], longer hospital stay [(15±6)d vs. (19±7)d; t=2.70, P=0.009], higher dyspnea ratio (5.41% vs. 53.85%; χ2=18.90, P<0.001), lower nasal oxygen therapy ratio (81.08% vs. 19.23%;χ2=23.66, P<0.001), and higher bi-level positive airway pressure ventilation ratio (0 vs. 57.69%; χ2=25.62, P<0.001). Time from onset was (23±6) days in severe/critical group, significantly longer than that in mild/moderate group [(18±7) days] (t=3.40, P<0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% vs.10.81%;χ2=4.24, P=0.039) and lower ground-glass opacities ratio (15.38% vs. 67.57%; χ2=16.74, P<0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% vs.34.61%; χ2=13.43, P<0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% vs.10.81%; χ2=20.47, P<0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points vs. 7 (4,9) points; Z=3.81, P<0.001]. Conclusions The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.

The Clinical Characteristics and Prognosis Factors of Mild-Moderate Patients With COVID-19 in a Mobile Cabin Hospital: A Retrospective, Single-Center Study.

Background: Novel mobile cabin hospitals have been built to provide more makeshift beds for patients with COVID-19 in Wuhan. However, the characteristics of these patients needed be further described. Methods: This was a retrospective, single-center study. A total of 869 patients with confirmed COVID-19 were admitted to Wuchang Mobile Cabin Hospital in Wuhan, between February 6th, 2020 and February 20th, 2020. The final date of follow-up was March 6th, 2020. Clinical characteristics and outcome data were collected and analyzed. Results: Of 869 patients, the median age was 51 years (IQR, 40-58 years), and 377 patients (377/869; 43.4%) were men. A total of 616 patients (616/869; 70.9%) were discharged, 95 patients (95/869; 10.9%) were transferred to the designated hospital due to worsening condition (endpoint), and 158 patients (158/869; 18.2%) were still in the hospital. The incidence of the main symptoms, including fever, cough, fatigue, muscle aches, and anorexia, decreased with time. However, there were no differences in outcome among the patients with different onset times. Generally, both patients aged 45 years or older and patients with comorbidities were more likely to reach the endpoint (transfer to designated high-level hospitals due to condition worsen). In the other model, patients with the lung CT feature (e.g., ground-glass opacity, reticular/linear, air bronchogram, or consolidation shadow) were more likely to reach the endpoint. Conclusion: Older age, comorbidity, special chest CT features (e.g., ground-glass opacity, reticular/linear, air bronchogram, or consolidation shadow) are associated with poor prognosis for mild-moderate patients. The initial symptoms of mild-moderate patients may become insidious, which deserves our attention.