The severe pneumonia caused by the human coronavirus (hCoV)-SARS-CoV-2 has inflicted heavy casualties, especially among the elderly and those with co-morbid illnesses irrespective of their age. The high mortality in African-Americans and males, in general, raises the concern for a possible X-linked mediated process that could affect the viral pathogenesis and the immune system. We hypothesized that G6PD, the most common X-linked enzyme deficiency, associated with redox status, may have a role in severity of pneumonia. Retrospective chart review was performed in hospitalized patients with COVID19 pneumonia needing supplemental oxygen. A total of 17 patients were evaluated: six with G6PD deficiency (G6PDd) and 11 with normal levels. The two groups (normal and G6PDd) were comparable in terms of age, sex, co-morbidities, and laboratory parameters—LDH, IL-6, CRP, and ferritin, respectively. Thirteen patients needed ventilatory support ; 8 in the normal group and 5 in the G6PDd group (72% vs.83%). The main differences indicating increasing severity in normal vs. G6PDd groups included G6PD levels (12.2 vs. 5.6, P = 0.0002), PaO2/FiO2 ratio (159 vs. 108, P = 0.05), days on mechanical ventilation (10.25 vs. 21 days P = 0.04), hemoglobin level (10 vs. 8.1 P = 0.03), and hematocrit (32 vs. 26 P = 0.015). Only one patient with G6PDd died; 16 were discharged home. Our clinical series ascribes a possible biological role for G6PDd in SARS-CoV2 viral proliferation. It is imperative that further studies are performed to understand the interplay between the viral and host factors in G6PDd that may lead to disparity in outcomes.
The novel coronavirus SARS-CoV2 that causes coronavirus disease 2019 (COVID19) has approximately afflicted over 72 million people worldwide [1,2,3,4], including approximately 16.2 million in the USA as of December 2020. Among 1482 patients hospitalized reported by COVID19–Associated Hospitalization Surveillance Network (COVID-NET), 74.5% were aged ≥ 50 years, and 54.4% were male [2, 5, 6]. The male predominance hints at X linked related differences in the predilection to the severity of illness. One such possibility is the X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd), the most common enzymopathy, commonly manifesting as hemolysis due to oxidative stress [7,8,9]. With over 200 mutations identified in G6PDd, mainly in the coding regions, causing various degrees of deficiency, it is found in high frequency among African Americans, Mediterranean, and Asians . The gene encoding G6PD is located near the telomeric region of the distal arm of the X chromosome (band Xq28), a well-documented hot spot of a group of genes that includes fragile X, color vision, hemophilia A, and congenital dyskeratosis . The G6PD gene results in many biochemical variants and the deficiency of the gene product-G6PD, which is the rate-limiting enzyme in the pentose-phosphate pathway [8, 9]. The variants are grouped into four classes: (a) Class I variants comprise the most severe form of G6PDd and lead to chronic non-spherocytic hemolytic anemia, and typically occurs with enzyme activity < 10% of normal; (b) Class II variants typically have < 10% residual enzyme activity, but no hemolytic anemia; and (c) Class III and IV variants (10–60% and 60–150% activity, respectively) have milder phenotypes and hemolysis occurs only after extreme oxidative stress . Very severe G6PDd is sporadic and rare, whereas less severe deficiencies are polymorphic, and more common in tropical areas, postulated to be evolved as protection against malaria [7, 8]. Males are more commonly affected when hemizygous and can be either phenotypically normal or deficient . Homozygous females are as deficient as the hemizygous males, whereas heterozygous females are mosaics with intermediate levels of deficiency as a result of random X-chromosome inactivation (lyonization) . We report here clinical scenarios of six COVID19 positive patients, with no previous respiratory issues with G6PDd, who required longer ventilatory support and ICU care compared to 11 matched controls. Given the role of G6PD in altering redox homeostasis , we hypothesize that the deficiency further enhances oxidative stress by uncontrolled production of reactive oxygen species (ROS) during this rapidly evolving inflammation caused by the SARS-CoV-2 virus and host immune system, leading to abnormal pulmonary vascular performance and respiratory decline. This case series warrants a systematic investigation of the role played by G6PD in this unrelenting COVID19-induced pneumonitis.
We reviewed the charts of 17 consecutive patients who were admitted to the Houston Methodist hospital and ICU with confirmed COVID19 infection, and where G6PD levels were available with consent, between March 15 and May 15, 2020. Clinical data were obtained through an Institutional Review Board (IRB) approved protocol PRO00025607 that allowed review of medical records. The main inclusion criteria included adults > 18 years old with a diagnosis of COVID19 within 24 h of admission to the hospital and where G6PD levels were obtained. G6PD was considered low if the recorded values were below the laboratory cut-off value of 9.6 U/g Hb; < 4.5 was considered severe, values between 4.5 and 9.6 as mild, and all other values as normal. Of note, G6PD testing as obtained as baseline in patients as hydroxychloroquine (HCQ) was the first line of treatment per the institutional protocol at the time of the study. Both groups received a 5-day course of HCQ and completed the course by the time G6PD result was reported. The G6PDd patients (3 severe and 3 mild) were compared to the normal cohorts (where the G6PD values were > 9.6) in 2:1 matching for age, gender, and co-morbidity. The data reported here have follow-up available through June 20, 2020; each patient had at least 21 days of follow-up.
Descriptive statistics were used to summarize the data; results are reported as means and medians, as appropriate. The unpaired t test was performed using GraphPad Prism 8 for macOS version 8.4.2 (464), April 7, 2020, GraphPad Software, San Diego California USA, www.graphpad.com. All comparisons were one-tailed; a P value of less than 0.05 was considered significant.
Corelation of weather parameters with COVID-19 spread and mortality rate
In this work, we explore the corelation of weather parameters with COVID 19 spread and mortality rate.
Here we are motivated to study the effect of weather conditions, area density and infection (case count) due to COVID-19, and mortality rate. We have used several machine learning models for exploring these relationships. We have used publicly available datasets from Kaggle for validations. The performance of the Machine learning regression models is measured using standard performance metrics.
Goals And Challenges
In this project, we first estimate the relation between different weather parameters and covid-19 spread and convert it to a model to forecast the spread of the virus at a time according to dependency upon other weather variables. This model takes a very correlational view of the data and explores the inter-zone differences in the virus spread. The seasonal nature of flu spread drives our modeling hypothesis, and associated weather variances inform our thinking on this hypothesis.
We are using weather differences across different zones/times to understand the correlations.However, lack of availabile long time series data at this point, is limiting our study to exploratory analysis.
Weather parameter : Temperature
Temperature VS covid cases
(color bar denotes temperature and size of bubble denotes the number of covid cases)
Graph for the dependency of covid confirmed case on weather parameters and other different factors using decision tree model
Feature importance graph for the dependency of covid deaths on weather parameters and other different factors using decision tree model
Heatmap plot for correlation between different variables used.
Yes, vaccines are very effective in tackling infectious diseases. Vaccine works by creating a memory about the pathogen and neutralizing it when it encounters the same pathogen again.
We will jump into more detail, but in a very simplified way. All figures quoted are approx, just give the extent of efficiency. Every virus, every lymphocyte behaves differently.
To understand how vaccines work, we need to understand how the body fights any pathogens. When the body is invaded by a pathogen, the body deploys first level defence innate immune cells. In most cases it is sufficient, but in some cases it is not and when the adaptive immune system kicks in (lymphocytes). If it is the first time then lymphocytes have to learn about pathogens and develop an antibody response which helps in tackling the pathogens. This counter attack is very precise and it targets pathogens like a guided missile. Since they have never seen the pathogen before, this process takes a while or the person may even die, before lymphocytes find the antibody. Once they encounter the pathogen, they also make memory of pathogens. If the pathogens come again, then lymphocytes, identify the pathogen faster and activate sooner, lot faster, let stay 10times or more .
Now here is where the vaccine comes into play. Vaccines are nothing but weakened pathogens, or it could be any part of pathogens (antigens). Once a vaccine is administered, the body undergoes the exact same response as detailed above. Weakened viruses (or just portions of virus) never could replicate, and hence a significantly large dose is given, so as to create lymphocytes response and creation of memory lymphocytes. Some cases multiple doses are required. If an actual virus invades the body, memory lymphocytes will get activated a lot faster and virus neutralized without even the patient knowing it. If we assume the virus kills 10%, then every 1000, 100 patients will die. Normally with a vaccine not a single patient would die in such a case, max may be 1 will get some adverse reaction. Vaccines are 99.99% effective in saving lives or preventing disability like polio virus.
There are many advantages about vaccines even if viruses don't kill the patient, sometimes the body does take time to produce a response and real viruses will destroy the body before that (example polio). There are also cases like coronavirus, where virus multiples and our own lymphocytes restore to nuking to kill the virus (cytokine storm), which do severe damages to lungs of humans and this is the main reason why humans are dying from coronavirus or even common flu. With a vaccine body will be trained in recognizing the virus and such eventuality will never arise. Also vaccines help us wipe out viruses completely, even if the death rate is less, as it can mutate anytime to become more dangerous or contagious. Also vaccine prevent random damages to body caused by virus, take example coronavirus, it can damages 1000+ place in body as it capable to bind to many places in body. Sometimes it leads to other diseases, cancer or life long problems. Sometimes the virus makes its way to the brain, eyes, nerves etc, which is out of reach for lymphocytes and can live there for a long long time. There are cases in coronavirus, where patients never get well, sometimes get sick, get better and get sick again.
It is never too late to take a vaccine, make sure to take your vaccine now. Also it is advisable to take every vaccine available as soon as it is available.
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