Coronaviruses are enveloped, single-strand, positive-sense RNA viruses.
They are large, enveloped, positive strand RNA viruses divided into four genera: alpha, beta, delta, and gamma of which alpha and beta coronavirus are known to infect humans.
Four coronaviruses are endemic globally and account for 10-30% of upper respiratory tract infections in adults.
Coronaviruses are distributed wrongly broadly among humans, mammals, and birds that cause respiratory, enteric, hepatic , and neurologic diseases.
Phenotypically and genotypically diverse viruses.
Widespread among mammals and birds.
But the widest varieties of genotypes infect bats, but two subtypes infect humans alpha and beta coronaviruses.
Beta coronaviruses include acute respiratory syndrome coronavirus-SARS-CoV, middle east respiratory syndrome coronavirus (MERS-CoV), and the coronavirus variant COVID-19.
Found in bats, birds, cats, dogs, pigs, mice, horses, whales, and human beings.
Its surface spike glycoprotein is critical for binding host cell receptors and is believed to represent a key determinant of infection.
In humans coronaviruses have short incubation periods, ranging from days for SARS and weeks for MERS, and the COVID-19 appearing to fall in between the two.
Associated with respiratory, enteric, hepatic, when neurologic diseases in various animal species.
Six coronavirus species are known to cause human disease.
4 Human coronaviruses cause respiratory infections and are known to be endemic.
For viruses-229E, OC43, NL63, and HKU 1 are prevalent and typically cause common colds in immunoincompetent individuals.
Usually associated with mild upper respiratory tract infections in adults but in immunocompromised patients can cause pneumonia.
Coronavirus-causes severe acute respiratory syndrome (SARS), and MERS-CoV.
SARS Symptoms include: fever, cough, dyspnea, and occasionally watery diarrhea.
Of SARS patients who get infected 20-30% require mechanical ventilation and 10% die, with higher mortality rates in older patients in those with medical comorbidities.
SARS resulted in 8098 infections and 774 deaths.
SARS Patients present with severe acute respiratory syndrome with fever, symptoms of lower respiratory tract infection with radiographic evidence of pneumonia or acute respiratory distress syndrome.
SARS disproportionately affects healthcare workers
SARS incubation is between two and 10 days.
SARS Diagnosis is based on PCR testing.
The sensitivity PCR testing with nasopharyngeal swabs is high and nearly 100%.
SARS Treatment includes corticosteroids in ribavirin but have not been found to be helpful.
Supportive care is the cornerstone of care for SARS.
MERS As of November 2019 cost a total of 2494 cases and 858 deaths, the majority in Saudi Arabia.
MERS Natural reservoir is thought to be bats.
MERS is associated with atypical pneumonia but more prominent gastrointestinal symptoms, and acute kidney failure.
MERS necessitates mechanical ventilation in 50-89% of patients and has a case fatality of 36%.
A novel coronavirus designated 2019-nCOV, SARS-CoV-2.
The viral genome reveals 75-80% identical to the Sars-COV and even more closely related to several bat coronavirus is.
Increasing number of cases have resulted from human-to-human transmission.
There have been more than 771 million cases and 6.9 million deaths in the coronavirus disease 2019 pandemic. (WHO).
More than 80% of people affected have a mild form of COVID-19.
The provisional leading cause of death ranking for 2020 indicated the Covid-19 was the third leading cause of death in the US behind heart disease and cancer.
In some cases the viral RNA can be detected by PCT even be on week six following the first positive test.
Attempts to isolate the virus and culture are not successful beyond day eight of illness, which correlates with the decline of infecting today beyond the first week.
The respiratory transmission of COVID-19 makes its spread very efficient.
Covid-19 is primarily transmitted from person to person through respiratory droplets that enter the nose, mouth, or eyes by contaminated hands.
The chances of transmission increase the longer an uninfected person stays in any enclosed space within infected person.
Infection can occur through a short range transmission of exhaled respiratory particles from an infectious person resulting in mucous membrane deposition or inhalation of exhaled respiratory particles by in an infected person, and also can occur through long range transmission from inhalation of infectious respiratory particles that remain suspended in air for longer periods: potentially after the infectious person is no longer present and across longer distances greater than a few meters.
If Covid-19 is primarily spread by respiratory droplets, wearing a mask, face shield while keeping 6 feet apart from other individuals should be adequate to prevent transmission.
Severe manifestations of Covid-19 infection are associated with an exaggerated immune response driven by interleukin-6, tumor necrosis factor alpha, and other cytokines in a pattern called a cytokine storm.
Centers for Disease Control and Prevention (CDC) recommends frequent handwashing, physical distancing of at least 6 feet, and the use of face masks to cover the mouth and nose.
If COVID-19 is carried by aerosols that can remain suspended in the air for prolonged periods medical masks would be inadequate because aerosols can both penetrate and circumnavigate masks, face shields would provide only partial protection because there are open gaps between the shield and the wearer’s face, and 6 feet of separation would not provide protection from aerosols that remain suspended in the air or are carried by currents.
Experiments support the possibility that Covid19 may be transmitted by aerosols even in the absence of aerosol generating procedures such as intubation or non-invasive positive pressure ventilation.
Speaking and coughing produce a mixture of both droplets and aerosols in a range of sizes, and the secretions can travel together for up to 27 feet, that is feasible forCovid-19 to remain suspended in the air and viable for hours.
Covid-19 RNA can be recovered from air samples in hospitals,
Epidemiologic evidence has demonstrated a pre-symptomatic and asymptomatic transmission of virus has driven the Covid-19 epidemic.
High rates of household transmission occurs because there is often limited wearing of masks and social distancing.
Symptoms may appear 2-14 days after exposure to -the virus:People with these symptoms may have COVID-19:
Fever or chills
Cough
Shortness of breath or difficulty breathing
Fatigue
Muscle or body aches
Headache
New loss of taste or smell
Sore throat
Congestion or runny nose
Nausea or vomiting
Diarrhea
Clinical spectrum of infection with Covid ranges from asymptomatic infection to critical illness.
The provisional leading cause of death ranking for 2020 indicated the Covid-19 was the third leading cause of death in the US behind heart disease and cancer.
Respiratory droplets are generated within the human respiratory tract, thoracic or extrathoracic, with possibly different pathogen loads, or upon release from an infected person via lung-fluid fragmentation.
Healthcare workers rarely acquire infections during patient care with proper personal protection equipment is used.
Respiratory droplets are expelled by expiratory events that include violent events such as coughing or sneezing and quiescent ones such as talking, breathing, or laughing.
Respiratory droplets have been associated with three modes of pathogen transmission: contact, droplet, and airborne transmission modes.
Contact transmission, direct or indirect, occurs via contact with pathogen-laden droplets: transfer of pathogens via physical touch between a susceptible and an infected host such as
hand contact; direct contact transmission.
Transfer mediated by fomites containing settled droplets is classified as indirect contact transmission.
Droplet transmission refers to transmission by large droplets (diameter >20 microns that are transported by the turbulent air flow generated by a violent expiratory event.
Subsequently droplets are sprayed and directly deposited upon the conjunctiva or mucus membranes of a susceptible host.
Large droplets settle rather quickly, droplet transmission is considered important at close range.
In still air, a 50-micron droplet crosses a vertical 1.5m distance in 20 seconds.
Airborne transmission, (aerosol transmission), refers to pathogen transmission via inhalation of small respiratory droplets that are typically smaller than 10 microns:
A 10-micron droplet settles in still air within approximately 9 min.
Aerosols are relatively small and may deposit deep into the respiratory tract, including the alveolar region.
These droplets, are small enough to remain airborne for sufficient time to transmit the pathogen.
Airborne transmission does not require direct face-to-face contact.
Droplets associated with droplet transmission may be transported by a turbulent jet and subsequently inhaled.
Respiratory-droplet diameters vary from 0.5 microns to 1000 microns.
Respiratory droplets are generated in a nearly 100% relative-humidity environment.
When exhalation into a lower-humidity ambient environment the respiratory droplets shrink by evaporation on the order of seconds or less, depending on droplet size, composition, and relative humidity to reach their equilibrium diameter.
It is estimated that droplets may shrink to about half their original size.
Droplets classically or larger entities that typically are grounded by forces of gravity within 3-6 feet of the source person.
Pathogen transmission depends on the interplay of a number of factors, including frequency of violent droplet-generating events such as coughing, sneezing, droplet size distribution, ambient relative humidity, viral load, virus inactivation rates, deposition location of inhaled droplets in the airway, and infectious dose.
Lymphopenia an elevated LDH levels are common with Covid-19 but are not specific.
There is no current evidence that Covid-19 is transmitted through food consumption.
Almost 41% of adults report at least one adverse mental or behavioral health condition including depression, anxiety, posttraumatic stress, and substance abuse, with rates that are 3-4 times the rates one year earlier.
The illness caused is milder than was seen during the SARS outbreak.
Fever, dry cough, shortness of breath, fatigue, or bodyaches are some of the most common symptoms.
Some patients experience headache, abdominal pain, diarrhea, and sore throat.
Symptoms usually appear to-14 days after exposure, although some patients may not develop symptoms until later.
Sudden onset of anosmia has been reported in Covid-19 infection.
Anosmia and ageusia have been reported in up to 68% of patients an are more common in women men and men.
It is likely to evolve much like H1N1, from a novel pandemic coronavirus strain to an endemic seasonal strain that causes about a quarter of cases of the common cold.
Covid-19 is spread primarily via respiratory droplets during close face-to-face contact.
The infection can be spread by asymptomatic, pre-symptomatic, and symptomatic carriers.
Covid-19 is primarily spread from person to person respiratory particles, probably a varying sizes.
Viral particles are released when an infected person coughs, sneezes, or speaks.
Both smaller particles by aerosol, and large particle droplets are concentrated within a few meters, and the likelihood of transmission decreases with physical distancing and increased ventilation.
Covid-19 infections are spread by respiratory particle transmission within a short distance when a person is less than 2 m from an infected person.
Covid-19 enters human cells by a key viral protein involved in cell entry, and the spike (S) protein is located on the surface of the virus particle.
Two host proteins, angiotensin-converting enzyme 2 and transmembrane protease serine S 2 are critical for cell entry.
The viral S protein binds to ACE2 which serves as the cell membrane receptor for Covid-19, but only after the S protein has been primed by the action of the serine protease.
The Covid-19 virus penetrates human cells through direct binding with ACE2 receptors on the cell surface.
Obese individuals have more ACE2 expression making them more vulnerable to Covid-19 infection.
ACE inhibitors in COVID-19 show a lack of benefit.
Aerosols can be generated during intubation, the use of nebulizers, talking, singing or shouting in poorly ventilated environments and in these situations transmission over longer distances may occur.
Covid-19 RNA has been detected in blood in stool, although fecal-oral spread has not been documented.
A small proportion of patients whose respiratory samples are negative for Covid-19 shed Covid-19 RNA in their feces, about 4% for at least seven months: these people are more susceptible to gastrointestinal symptoms.
Acutely infected patients shed Covid-19 through the feces in about 40 to 85% of fecal samples.
COVID-19 is associated with a 25% higher risk a later being diagnosed with autoimmune inflammatory rheumatoid disease.
In laboratory conditions Covid-19 may persist on cardboard, plastic stainless steel, and contamination of inanimate services has been proposed to play a role in transmission, but its contribution is uncertain and may be relatively small.
Laboratory findings in hospitalized patients with Covid-19 include: lymphopenia, elevated D-dimer levels, LDH, C reactive proteins, and ferritin.
Procalcitonin levels are typically normal at presentation of Covid-19 patients.
Laboratory findings associated with poor outcomes include: an increasing white blood cell count with lymphopenia, prolonged prothrombin time, elevated levels of liver enzymes, LDH, D-dimer, interleukin-6, C reactive proteins, and procalcitonin.
The average time from exposure to symptoms onset is five days, and 97.5% of patients who develop symptoms will do so within 11 1/2 days.
Patients may be infectious 1-3 days before symptoms onset.
Up to 40-50% of cases may be aTtributable to transmission from asymptomatic or pre-symptomatic people.
In the US, approximately 8% of persons are hospitalized after infection with severe acute respiratory syndrome due to Covid-19.
Just before and soon after symptom onset, patients have high nasal pharyngeal virus levels, which then fall over a period of 1-2 weeks.
Patients may have detectable Covid-on polymerase-chain � reaction (PCR) tests for weeks to months, but detecting viable virus and contact tracing suggest that the duration of infectivity is much shorter.
The PC or testing for Covid-19 amplifies targeted nucleic acid sequences to detect SARS-Covid-2 RNA.
RT-PCR testing detects SARS-Covid-2 RNA at low levels, with analytic sensitivity of 98% and specificity of 97%.
Clinical sensitivity is approximately 9% and clinical specificity is approximately 95%.
Immune competent adults are not infectious more than 10 days after symptom onset, but RT-PCR testing can detect manufactures viral RNA up to 12 weeks after infection.
Antigen tests are less sensitive than RT-PCR but better predict contagiousness.
Current recommendations for lifting isolation in most patients is 10 days after symptom onset of fever has been absent for at leaden 24 hours and other symptoms have decreased.
The evaluation of close contacts of patients with confirmed Covid-19 report that only 5% of contacts become infected.
The spread of Covid-19 even among close contacts varies with the duration and intensity of the contact.
The risk among household members of transmission rates range between 10 and 40%.
Individuals with close but sustained contacts, such as sharing meals associated with the secondary attack rate of about 7%, whereas passing interactions among people shopping is associated with a secondary attack rate of 0.6 %.
COVID-19 most common comorbidities are hypertension, obesity, and diabetes.
Postural tachycardia syndrome symptoms are seen in people with postacute sequel of COVID-19: also reported as a complication of Covid-19 vaccine.
The presence of obesity, type two diabetes, chronic kidney disease or cardiovascular disease are known risk factors for severe illness from Covid-19 in persons of any age.
With obesity there is more than 113% increase in the likelihood of going into the hospital and 50% more likelihood of dying from Covid-19.
Risk factors for complications of Covid-19 include: older age, cardiovascular disease, chronic lung disease, diabetes, and obesity.
Black, Hispanic, American Indians, Alaskan natives, and Pacific islanders have increased increased rate of infection and disproportionately poor outcomes from Covid-19, including higher risk of death than white individuals.
Black, Indigenous, and Latin people have a higher risk for poor outcomes: blacks are hospitalized 2.3 times the rate and died at 1.7 times the rate of White people and Hispanic people have been hospitalized 2.2 times the rate and died at 1.8 times the rate of White people.
Black, Indigenous, and Latin people have died from COVID-19 at younger ages than white people on average.
In a recent study of 5700 patients hospitalized, 14.2% were treated in the ICU, 12.2% received invasive mechanical ventilation, and 3.2% were treated with kidney replacement therapy, and 21% died (Northwell).
Approximately 20% of symptomatic patients develop moderate-severe pneumonia and require hospitalization.
Approximately 20-30% of patients require ICU care for respiratory support, and more than 15% of patients with severe pneumonia developed acute respiratory distress syndrome.
Histologically ARDS in Covid-19 has diffuse alveolar damage with edems, hemorrhage, and intraalveolar fibrin deposition.
The portal for Covid-19 is inhalational, and alveolar infiltrates are commonly found on chest x-ray or CT scan, the respiratory distress includes vascular insults that potentially mandates a different treatment approach than customary is applied for ARDS.
Patients with Covid-19 and ARDS may eventually develop multi organ failure.
Among patients with Covid-19 infection men have a significantly higher mortality rate than women, and the difference is not completely explain by the higher prevalence of comorbidities in men.
Covid-19 is a systemic disease that primarily injures vascular endothelium.
The R0 for COVID-19 is a median of 5.7, according to a study, about double an earlier R0 estimate of 2.2 to 2.7
SGLT2 inhibitors drugs should be held during Covid-19 infections due to a higher incidence of diabetic ketoacidosis.
D-dimer levels of greater than two times the upper limit of normal is an independent risk factors for in hospital mortality in patients with Covid-19.
D-dimer is a an important biomarker from a prognostic point of view for Covid-19, as are other pro inflammatory cytokines including interleukin 6, granulocyte colony stimulating factor, and tumor necrosis factor alpha.
Patients commonly experience thromboembolic manifestations involving the venous and microvasculature system, especially the pulmonary endothelium vasculature.
In critically ill patients with Covid-19 therapeutic anticoagulation with heparin did not result in greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual care.
Among critically ill patients with Covid-19 treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support free days, within 21 days.
The inflammatory response to Covid-19 infection commonly results in marked activation of coagulation and thromboinflammation with evidence of systemic endothelial damage and result in loss of normal anticoagulant properties.
With acute endothelial dysfunction and coagulopathy platelets are hyperactive with increased responsiveness to activation stimuli and have altered gene expression profiles and phenotypic changes indicative of abnormal platelet leukocyte interactions.
The use of anti-platelet drugs has not been found to be efficacious in the preventing thromboembolism in Covid-19.
Trials suggest that prophylactic anticoagulation with heparin reduces the risk of thromboembolism in Covid-19.
A metaanalysis of hospitalized patients with Covid-19 estimated an overall venous thromboembolism prevalence of 14%,-8% in non-critically ill patients versus 22.7% in patients requiring ICU level care.
Non-hospitalized patients who are immobile and require oxygen therapy may benefit from prophylaxis with low molecular weight heparin.
Non-critically ill hospitalized patients with low bleeding risk and elevated D-dimer who require a supplemental oxygen benefit from therapeutic anticoagulation.
Critically ill hospitalized patients should be treated with prophylactic low-dose low molecular weight heparin or unfractionated heparin.
In non-critically ill patients with Covid-19 a strategy of therapeutic dose anticoagulation with heparin increase the probability of survival to hospital discharge with reduce use of cardiovascular or respiratory organ support as compared with usual care thromoprophylaxis.
Anti-phospholipid autoantibodies have been detected in 30-52% of samples of patients with severe Covid-19 accounting for the predisposition to thromboembolism.
SARS-CoV-2 enters the cell with the angiotensin converting enzyme type 2 receptors which is espressed by pneumocytes and leads to the down regulation of ACE-2 levels.
The pathogenesis of Covid-19 disease involves tissues which express high levels of ACE2 receptor.
Covid-19 infection typically starts in the oropharynx or nasopharynx, and then spreads to tissues that express ACE2 with involvement of the upper airway and lungs occurring, potentially leading to pneumonitis.
It is suggested that nearly half of the severe acute respiratory syndrome coronavirus – 19 transmissions occur before the onset of symptoms.
The development of anti-spike or anti-nucleocapsid IgG antibodies In patients with Covid-19 infection substantially reduces the risk of re-infection in the ensuing six months.
In a randomized clinical trial of 659 patients hospitalized with mild-moderate Covid-19 who were taking an ACE inhibitor pr ARBs before hospital admission: the mean number of days alive and out of the hospital for those assigned to discontinue versus continue these medications was not statistically different.
Available evidence indicates that SARS-CoV2 enters the central nervous system through the lymphatic system and the virus was confirmed present in the capillaries and neuronal cells of the frontal lobe of COVID-19 patients.
This is corroborated with evidence demonstrating that SARS-CoV2 was present in cerebral spinal fluid of infected patients which displayed severe neurological symptoms.
Covid-19 infection rate is more than three fold higher in predominantly black counties than in a predominately white counties.
The COVID-19 death rate for predominantly black counties is six fold higher than predominantly white counties.
The highest reported mortality rates from Covid-19 was found in American Indian and Alaskan natives, Black, and Hispanic populations.
During the COVID-19 pandemic, the risk of homicide-suicide among older adults may be increased due to several factors, including, physical distancing and quarantine measures.
The higher rate of infection, severe complications, and death among people of color, in particular, are at least in part due to social determinants of health: housing, transportation, education, access to healthcare, healthy food option availability, secure income, and freedom from structural and institutional barriers.
People who are addicted to drugs or other substances are more likely to contract COVID-19 and to be hospitalized or die from it (National Institutes of Health).
Those with a recent opioid use disorder diagnosis were most likely to develop COVID-19, followed by people with tobacco use disorder.
Basic management includes antipyretics, analgesia, fluid and electrolyte balance, and oxygen supplementation.
COVID-19 infection-approximately 8% of patients will require endotracheal intubation and mechanical ventilation.
Blood type O associated with lower risk to COVID-19.
RH positivity is associated with a higher risk of Covid-19.
Mail-to-female case fatality ratio ranges from 1.6-2.8 among Covid-19 patients.
Anti-COVID-19 antibodies are detectable in the majority of patients 14 days or more after development of symptoms.
Antibody testing in general is reserved for people who are suspected to have Covid-19 but have negative PCR testing and in. whom symptoms began at least 14 days earlier.
PCR positivity in sputum and stool compared to nasal pharyngeal specimens and may last a much longer period of time.
PCR positivity is highest in bronchoalveolar labage specimens, followed by sputum, nasal swab and pharyngeal swab.
PCR specificity is 100% because the test is specific to the genome sequence of Covid-19.
The most sensitive and the earliest serological marker is totally antibodies, levels of which begin to increase from the second week of symptom onset.
Antibodies against SARS-COV-2 continue to evolve up to a year after infection, and vaccines improve the immune response.
Covid-19 vaccine substantially enhances the immune response to variants among patients with prior infection.
There is no significant association between vaccination with mRNA Covid-19 vaccines and selected serious health outcomes 1-21 days after vaccination.
COVID-19 is asymptomatic in one in five people with Covid-19, and they are likely to have a common variant or allele HLA B15:01.
The risk of myocarditis after receiving mRNA based COVID-19 vaccines is increased across multiple age and sex strata and is highest after the second vaccination dose in adolescent males and young men.
Vaccination with an mRNA Covid-19 vaccine is significantly less likely among patients with Covid-19 hospitalization and disease progression to death or mechanical ventilation.
Vaccination of previously infected individuals will be most likely protected against the large array of circulating viral strains, including delta variant.
Only modest differences in vaccine effectiveness are noted with delta variant as compared with the alpha variant after receipt of two vaccine doses.
In Israel the administration of the BNT162b2 messenger RNA vaccine (Pfizer) was is associated with myocarditis, an incidence of 2.1 cases per hundred thousand persons. with the highest incidence among male patients between the ages of 16 and 29 years: most cases are mild or moderate in severity.
Vaccine studies from Israel revealed there a booster received at least five months after a second dose of vaccine reduced mortality by 90% from COVID-19 than in participants who did not receive the booster and similarly, studies indicated such findings across all age groups.
In a large population based study, vaccination of pregnant individuals with mRNA Covid-19 vaccine was not associated with increased risks of neonatal adverse events in their infants (Norman M).
IgM and IgG ELISA have been found to be present even as early as the fourth day after symptom onset, higher levels occur in the second and third weeks of illness.
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses:
Casirivimab and imdevimab are monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells.
Neutralizing monoclonal antibodies bamlanivimab and etesevimab lowered the incidence of COVID-19 related hospitalization and death among high-risk ambulatory patients compared to placebo.
In a clinical trial of patients with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalization or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo.
Investigational agent monoclonal antibodies tixagevimab and cilgavimab (Evsheld) can be administered by IM injection for preexposure prophylaxis of COVID-19 in persons 12 years or older with a history of severe allergy that prevents vaccination against COVID-19 of moderate or severe immune compromise.
Hydroxychloroquine in Covid-19 was not associated with either a greatly lowered or an increased risk of intubation or death.
Hydroxychloroquine with azithromycin, compared with neither treatment was not significantly associated with difference in hospital mortality in patients with Covid-19.
After high risk or moderate-risk exposure to COVID-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as a post exposure prophylaxis within four days of exposure (Boulware DR).
Pregnant women may be a greater risk for Covid-19 infection with more severe symptoms and worse pregnancy outcomes: higher risk of preterm birth and preeclampsia, as well as higher rates of cesarean section.
Among 6012 pregnant individuals with Covid-19 in Canada, infection was significantly associated with increased risk of adverse maternal outcomes in preterm birth.
Covid-19 vaccination is recommended during pregnancy: Studies of over 250,000 patients revealed Covid-19 vaccines during pregnancy are safe.
Early treat with molinupiravir reduces the risk of hospitalization of death in unvaccated adults with Covid–19.
Multi system inflammatory syndrome and children associated with Covid-19 can lead to serious and life-threatening illness in previously healthy children and adolescents.
Among patients with severe Covid-19 treatment with a seven day fixed course of hydrocortisone or shock-dependent dosing of hydrocortisone compared to no hydrocortisone suggested no superiority of the regimens (REMAP-CAP trial).
Among patients with Covid-19 and moderate or severe ARDS the use of intravenous dexamethasone plus standard care compared with standard care alone resulted in as the distinctly significant increase in the number of ventilator free days over 28 days (Tomazinin B).
The Recovery Collaborative Group found hospital hospitalized patients with Covid-19 the use of dexamethasone resulted in a lower 28 day mortality among those who receiving either invasive mechanical ventilation or oxygen alone, but not among those receiving no respiratory support.
A prospective meta–analysis of clinical trials of critical ill patients with Covid-19, the administration of systemic corticosteroids, compared with usual care or placebo was associated with a lower 28 day all cause mortality (REACT working group).
Treatment with inhaled steroids for 14 days does not result in shorter time to recovery, than placebo among patients with COVID-19 in the US. (ACTIVE Study group).
Low-dose hydrocortisone does not significantly reduce treatment failure in patients with COVID-19 related acute respiratory failure (Cape Cod COVID trial group).
The use of ACE inhibitors and ARBs is significantly more frequent among patients with Covid-19 because of their higher prevalence of cardiovascular disease, but there is no evidence that such agents affect the risk of Covid-19.
Prior ACE/ARB use is not significant associated with Covid-19 diagnosis of mortality among patients diagnosed as having Covid-19 (Fosbel E).
Remdesivir shortens Covid-19 recovery time from 15 days in a placebo group to 11 days.
Among non-hospitalized patients who were at high risk for Covid-19 progression a three day course of remdesevir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo.
Meta-analyses of randomized clinical trials and matched-control data demonstrated that COVID-19 patients transfused with convalescent plasma exhibited a lower mortality rate compared to patients receiving standard treatments.
Early transfusion,within 3 days of hospital admission, of high-titer plasma is associated with lower mortality.
Among patients with moderate Covid-19 those randomized to attend a course of remdesivir did not have a significant difference in clinical status compared to standard care at 11 days after initiation of treatment (Spinner CD).
Remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay (WHO).
Among predominantly vaccinated outpatients with COVID-19 the incidence of hospitalization or emergency department visit observation for greater than six hours), was significantly lower in patients, who received a single dose of pegylated interferon lambda than among those who receive placebo.
Among patients hospitalized for Covid-19, adding the anti-inflammatory drug baricitinib to remdesivir was associated with reduced time to recovery and faster improvement in clinical status in a second phase of the pivotal Adaptive Covid-19 Treatment Trial (ACTT).
Tocilizumab an anti-Interleukin-6 receptor antibody used in treating patients with Covid-19 pneumonia reduced the likelihood of progression to mechanical ventilation or death, but did not improve overall survival.
In critically ill patients with Covid-19 patients on supportive therapy with Interleukin-six receptor antagonists tocilizumab and sarilumab improve outcomes, including survival.(REMAP-CAP Investigators).
In a randomized trial of hospitalized patients with severe Covid-19 pneumonia the use of tocilizumab did not result in significantly better clinical status or lower mortality then to placebo at 28 days (Rosas I O).
The recruitment of neutrophils in COVID-19 is a key factor in the severity of cases .
Quantitative reverse-transcriptase-polymerase-chain reaction assays can rapidly detect the virus.
Covid-19 reverse transcriptase polymerase chain reaction testing may be associated with false negative results it up to 20-67% of patients dependent on the quality and timing of testing.
The RT-PCR test is performed using nasal pharyngeal swabs or other upper respiratory tract specimens, including throat swab, or more recently saliva.
RT-PCR Gene targets are used involving the envelope, nucleocapsid, spike, RNA-dependent RNA polymerase, and ORF1 genes.
In most individuals with symptomatic Covid-19 infection, viral RNA in the nasal pharyngeal swab is measured becomes detectable as early as one day of symptoms and peaks within the first week of symptom onset.
A positive PCR results reflects the detection of viral RNA and does not necessarily indicate presence of viable virus.
With sample testing, RNA is collected that is part of the virus particle, it is extracted and converted to complementary DNA for testing, the PCR test involves binding sequences on the DNA that only are found in the virus and repeatedly copying everything in between.
The above process is repeated many times and a fluorescent signal is created when amplification occurs and once the signal reaches a threshold, the test result is considered positive.
If no viral sequence is present, amplification will not occur, and the test will be negative.
Serologic assays allow assessment of the prevalence of the infection.
Pediatric inflammatory multi system syndrome has been described in association with Covid-19 infection and has overlapping clinical features with Kawasaki disease.
There has been a sharp increase in overdose-related cardiac arrests in the United States during the COVID-19 pandemic.
A study suggests patients using metformin before a diagnosis of COVID-19 only had a third of the mortality risk of their counterparts with no reported use of the drug.
Assuming no population immunity and that all individuals were equally susceptible and equally infectious, herd immunity threshold for Covid-19 would be expected to be in the range between 50 and 67% in the absence of any interventions.
A two dose regimen of mRNA Covid-19 vaccine by Pfizer confers 95% protection in person 16 years of age or older, with the safety similar to other viral vaccines. (BNT162b2).
Side Effects From the COVID-19 Vaccine –most commonly reported symptoms were headache (22.4%), fatigue (16.5%), and dizziness (16.5%).I
B.1.1.7 variant of Covid virus is more infectious than Covid-19.
No obvious safety signals have occurred among pregnant persons who received mRNA Covid-19 vaccines.
Side Effects From the COVID-19 Vaccine most commonly reported symptoms were headache (22.4%), fatigue (16.5%), and dizziness (16.5%).
More women than men report side effects from Covid-19 vaccine.
More women report side effects from the vaccine, may be due to their immune system being more reactive.
There is a point at which the number of lives lost from economic, social, and psychological factors of healthcare policy for Covid-19 that outweigh the number of lives lost from infection.
Health insurance claims for the emotionally turbulent years from 13-18, and to a somewhat lesser extent on those ages 19-22 they were sharp spikes from pre-pandemic levels in psychological conditions including: major depression, generalized anxiety disorder, adjustment disorder, self worm, substance abuse, overdoses, OCD, ADHD and tic disorders.
There was a 334% spike in intentional self harm among 13-18 year olds in the Northeast.
The most common symptoms after acute Covid-19 are fatigue and dyspnea, along with other common complaints of joint pain and chest pain.
Complications of Covid-19 could be the result of direct tissue invasion by the virus, profound inflammation and cytokine storm, related immune system damage, a hypercoagulable state and or a combination of these factors.
3/4 of patients hospitalized with Covid-19 still have at least one symptom six months after they became ill.
Covid-19, like other RNA viruses constantly changes through mutation, with new variance occurring over time.
Only a small number of Covid-19 variants are of public concern because they are more transmissible, cause more severe illness, or can allude immune response following infection in possibly vaccination.
80% of more than 200 patients hospitalized with COVID-19 had a vitamin D deficiency.
Among hospitalized patients with Covid-19, a single high dose of vitamin D3 compared with placebo did not significantly reduce hospital length of stay and its use is not supported for the treatment of moderate to severe COVID-19.
An estimated 42% of Americans have a vitamin D deficiency, according to statistics presented by the Cleveland Clinic in 2018.
A study showed 80% of more than 200 patients hospitalized with COVID-19 had a vitamin D deficiency.
Ivermectin use did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or prolonged emergency department observation among patients with an early diagnosis of Covid-19 (Reis G).
In a cohort study of 4638 individuals with a measured vitamin D level in the year before undergoing COVID-19 testing, the risk of having positive results in Black individuals was 2.64-fold greater with a vitamin D level of 30 to 39.9 ng/mL than a level of 40 ng/mL or greater, decreasing by 5% per 1 ng/ mL increase in level among individuals with a level of 30 ng/mL or greater.
There were no statistically substantial correlations between vitamin D levels with COVID-19 positivity rates in White individuals.
The habitual use of vitamin D supplements is substantially correlated with a 34% lower risk of COVID-19 infection.
Circulating vitamin D levels at baseline or genetically predicted vitamin D levels were not linked with the risk of COVID-19 infection.
The investigators concluded that their findings imply that habitual use of vitamin D supplements is related to a lower risk of COVID-19 infection.
In hospitalized patients with Covid-19 vitamin C had low probability of improving the primary composite outcome of organ support and free days in hospital survival.
There is tentative evidence fluvoxamine might be useful for reducing COVID-19 disease severity if given as an early treatment.
Hospitalized patients with COVID-19 and low vitamin D levels could have a decreased risk of dying or needing mechanical ventilation if they obtain at least 1000 units of vitamin D supplementation weekly.
Humoral immunity to coronavirus includes antibodies that bind the spike proteins and either neutralize the virus or eliminate it through other effective mechanisms.
Cellular immunity to coronavirus includes virus specific B cells and T cells, which provide long-term immunologic memory and rapidly expand on the exposure to antigen.
B cells produce antibodies, CD8 positive T cells directly eliminate virally infected cells, and CD4 positive T cells provide help to support the immune system.
Covid-19 brain scans and cognitive scores show: there is a loss grey matter thickness in the orbitofrontal cortex and para hippocampal gyrus associated with the sense of smell, tissue damage in areas connected with primary olfactory cortex, decreasing whole brain volume and increasing CSF volume and decline in the ability to perform complex tasks associated with atrophy in the crus II in the area of the cerebellum associated with cognition.
About 60% more easily passed from person to person than the Alpha version or B.1.1.
The basic reproduction number around six for Delta, meaning that, on average, each infected person spreads the virus to six others.
The delta variant is the most able and fastest and fittest of such viruses.
Patients with Covid-19 have increased risk of cardiovascular problems including abnormal heart rhythms, heart muscle inflammation, blood clots, strokes, myocardial infarction, and heart failure at one year after infection.
SARS-CoV-2 can directly infect and replicate in coronary arteries, promoting plaque inflammation, atherosclerosis, and cardiovascular risk.
In young children, with high, genetic risk of type one diabetes, Covid-19 infection was temporarily associated with the development of islet autoantibodies.
Casirivimab and imdevimab administered together are authorized for the treatment of mild to moderate COVID-19 in adults, as well as in pediatric patients at least 12 years of age and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19 and/or hospitalization.
Treatment of patients with symptomatic Covid-19 with nirmatrelvir plus ritonavir (Paxlovid) resulted in the risk of progression of severe Covid-19 that was 89% lower than the risk with placebo.
Nirmatrelvir plus ritonavir (Paxlovid)is effective against the omicron variant.
Among 1288 patients who received at least one dose of Nirmatrelvir/Ritonavir (Paxlovid) or placebo, time to sustained alleviation of all signs and symptoms of Covid – 19, did not differ significantly between participants who receivedNirmatrelvir/Ritonavir (Paxlovid) and those who receive placebo (Hammond JF).
A placebo control trial, post exposure prophylaxis with Nirmatrelvir/Ritonavir did not significantly reduce the risk of symptomatic COVID-19 infection.
Maternal vaccination with the mRNA vaccine is associated with reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than six months of age.
Observation studies of 1.2 million individuals with symptomatic Covid-19 infection rate the proportion of individuals with long Covid symptoms was 6.2%, including including 3.7% with ongoing respiratory problems and 2.2% for persistent fatigue with bodily pain or mood swings, and 2.2% for cognitive problems.
Among critically ill patients with COVID-19 randomized to receive an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180 day mortality compared with patients randomized to a control group, and treatment with an anti-platelet agent had 95% probability of improved 180 day mortality compared with a randomized control group.
More than 658 million people worldwide have been infected with Covid-19.
Post acute sequelae of COVID-19, also known as long Covid, is defined as ongoing, relapsing, and new symptoms or conditions present 30 or more days after infection.
Covid-19 surveillance of wastewater correlates with the number of hospitalizations and deaths from Covid-19.
At the end of 2022, and estimated 97% of people age 16 years or older had infections were vaccination induced antibodies.
Death rate was 61.3 per 100,000 persons from Covid in 2022.
Hybrid immunity of vaccination plus infection provides the most best protection against severe disease, hospitalization, and death.
The prevalence of hybrid immunity is the lowest amount of those 65 years and older, and immunity for vaccine wains overtime, and that decreases faster among older adults.
The secondary attack rate among household contacts of persons with early COVID-19 was approximately 10 to 12%: With the emergency of Delta and Omicron variants this estimate was up to 58 and 81%, respectively.