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» Home » CAD » Infectious Disease » Bacterial Infections » Coronavirus (COVID-19)
Background
COVID-19, caused by SARS-CoV-2, has caused a massive global health crisis since its emergence in Wuhan, China, in late 2019. This highly infectious respiratory virus has spread rapidly across the globe, leading to millions of deaths worldwide. The pandemic prompted the World Health Organization to declare a global emergency and take immediate measures to curb the spread of the virus. As an RNA virus, SARS-CoV-2 has a high rate of genetic evolution and is prone to developing mutations over time.
These mutations have resulted in several virus variants, some of which have been designated as variants of concern (VOCs) by the WHO. These VOCs have different characteristics than the original strain of the virus, such as increased transmissibility or the ability to evade the immune response. Some of the most well-known VOCs include the B.1.1.7 variant, first identified in the UK, the B.1.351 variant, first identified in South Africa, and the P.1 variant, first identified in Brazil.
These variants have spread rapidly and have caused concern due to their potential to increase the severity of COVID-19 or render current vaccines less effective. The emergence of VOCs highlights the importance of continued surveillance and monitoring of the virus to identify any new variants that may arise. It also underscores the need for continued efforts to prevent the spread of COVID-19, including vaccination, physical distancing, mask-wearing, and other public health measures.
Epidemiology
The World Health Organization has warned that viral diseases pose a significant public health risk, as evidenced by the emergence of several epidemics caused by viruses in the last two decades. These include the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002-2003, H1N1 influenza in 2009, and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The latest viral disease to significantly impact global health is COVID-19, caused by the SARS-CoV-2 virus, which has spread to 223 countries, resulting in over 593 million cases and more than 6 million deaths reported globally as of March 2023.
The WHO has reported that over 200 countries worldwide have reported SARS-CoV-2 variants of concern (VOCs). The Omicron VOC is the most dominant currently circulating variant since its first identification in November 2021. The United States has reported the highest number of SARS-CoV-2 infections and COVID-19-related deaths, followed by India and Brazil. In 2020, COVID-19 was the third leading cause of death in the United States after heart disease and cancer, with approximately 375,000 deaths reported.
According to the WHO, the case fatality rate for COVID-19 is estimated to be 2.2%. However, this rate is affected by several factors, such as age, preexisting medical conditions, and the severity of illness, which may vary significantly between countries. All age groups are at risk of contracting the infection, but individuals aged 60 years and above. Individuals with underlying medical comorbidities such as obesity, chronic lung disease, cardiovascular disease, chronic kidney disease, diabetes, smoking, cancer, and solid organ or hematopoietic stem cell transplant patients are more likely to develop severe COVID-19 infection.
Additionally, males have a higher risk of severe illness and mortality from COVID-19 than females, as reported by a retrospective cohort study from March 1 to November 21, 2020, of 42,604 confirmed SARS-CoV-2 patients in 209 US acute care hospitals. Furthermore, a recent CDC analysis of approximately 300,000 COVID-19 patients hospitalized from March 2020 to December 2020 found that racial and ethnic minority groups had a higher percentage of COVID-19-related hospitalizations than White patients, primarily due to increased exposure to the virus and a higher risk of developing severe disease.
Anatomy
Pathophysiology
SARS-CoV-2 is a viral respiratory infection that primarily targets the respiratory and vascular systems. The virus enters host cells by binding to ACE2 receptors, which are found on the respiratory epithelium and other organs such as the esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, and urothelial cells of the bladder. The spike protein S2 subunit is primed by the host transmembrane serine protease 2 (TMPRSS2) to facilitate cell entry and subsequent viral replication endocytosis.
The early phase of the illness involves direct virus-mediated tissue damage, while the late phase triggers an immune response with the release of cytokines such as TNF α, GM-CSF, IL-1, IL-6, IL-8, IL-1β, IL-12, and IFN-γ. In severe cases, an overactive immune response results in a cytokine storm characterized by high levels of cytokines, particularly IL-6 and TNF-α, which cause a local and systemic inflammatory response.
In severe cases, the increased vascular permeability and subsequent development of pulmonary edema are caused by multiple mechanisms, including endotheliitis, dysregulation of the RAAS, activation of the kallikrein-bradykinin pathway, and enhanced epithelial cell contraction. The binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of pro-IL-1β, which is cleaved into the active mature IL-1β that mediates lung inflammation, leading to fibrosis.
Etiology
Coronaviruses are positive-stranded RNA viruses with crown-like appearance under an electron microscope due to spike glycoproteins on their envelope. They belong to the Coronaviridae family and are classified into four genera: Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus. Betacoronavirus is further divided into five sub-genera.
AlphaCoVs and betaCoVs originate from bats and rodents, while deltaCoVs and gammaCoVs are believed to come from avian species. CoVs have become major pathogens in emerging respiratory disease outbreaks, causing respiratory, enteric, hepatic, and neurological diseases in animals such as cattle, camels, cats, and bats.
Despite their origins in animals, these viruses can cross species barriers and cause illnesses in humans, ranging from the common cold to severe diseases like MERS and SARS. So far, seven humans CoVs capable of infecting humans has been identified. Some were identified in the mid-1960s, while others were detected more recently. In general, about 2% of the population is estimated to carry CoVs without experiencing symptoms, and these viruses are responsible for approximately 5% to 10% of acute respiratory infections.
Genetics
Prognostic Factors
The outcome of COVID-19 is determined by various factors, including the patient’s age, the severity of symptoms at the time of diagnosis, any pre-existing health conditions, the speed at which treatment is provided, and how the patient responds to treatment. According to the World Health Organization, the global case fatality rate for COVID-19 is estimated at 2.2%.
However, the rate can be influenced by factors such as age, pre-existing conditions, and the severity of the illness. A multicenter study conducted in Europe on 4000 critically ill COVID-19 patients found a 31% mortality rate within 90 days, with a higher mortality rate among the elderly, diabetic, obese, and those with severe acute respiratory distress syndrome.
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
Hospitalized patients:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2: 100mg IV every day
Treatment duration:
Without ECMO/mechanical ventilation-5 days
With ECMO/mechanical ventilation-10 days
Non-hospitalized patients:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2 to 5: 100mg IV every day
Dose Adjustments
Renal impairment
eGFR≥30ml/min-No dosage adjustment necessary
eGFR<30ml/min-Not recommended
Hepatic impairment
Uncertain if dosage modification is necessary
Intravenous:
casirivimab-600mg, Imbdevimab-600mg: Single dose
SC: casirivimab-600mg, Imbdevimab-600mg: Single dose
Initial dose:
Tixagevimab-300mg IM
Cilgavimab-300mg IM administer consecutively
Dosing for patients who received 150 mg of tixagevimab and 150 mg of cilgavimab at the beginning
≤3 months since the initial dose -administer 150 mg tixagevimab
and 150mg cilgavimab
>3 months since the initial dose - administer 300mg tixagevimab
and 300mg cilgavimab
Repeat dose- Tixagevimab 300mg and Cilgavimab 300mg IM every six months
Indicated for COVID-19 Disease Prevention:
Full FDA clearance date: August 23, 2021)
Indicated for active vaccination against the coronavirus disease 2019 (COVID-19), which is brought on by the coronavirus 2 causing severe acute respiratory syndrome (SARS-CoV-2)
Primary 2-dose series:
0.3 mL (30 mcg) IM twice, given three weeks apart
provide a third main dosage at least 4 weeks following the second dose if the patient has a moderate or severe immunosuppression
Monovalent-Pfizer Vaccine
The Pfizer-BioNTech vaccine is a monovalent vaccine, which means it is designed to protect against a single strain of the SARS-CoV-2 virus
The vaccine may come in vials with either a purple cap (indicating that the vaccine needs to be diluted before use) or a gray cap (indicating no dilution is necessary)
Each dose of the vaccine contains 30 micrograms (mcg) of the vaccine in a volume of 0.3 milliliters (mL)
The vaccine is given in two doses, with the second dose administered 3 to 8 weeks after the first dose
A third dose (0.3 mL) may be given at least four weeks after the second dose for additional protection
Bivalent-Pfizer vaccine
For individuals 12 years of age and older, the vaccine was authorized for a two-dose primary series, with the second dose administered three weeks after the first dose
The vaccine was also authorized for a third dose as a booster shot for individuals 18 and older who had completed the two-dose primary series at least six months prior and were at increased risk of COVID-19 due to underlying medical conditions, occupational or institutional exposure or age
Booster Dose
At least two months following the first immunisation or the most recent booster dose with any authorized/approved monovalent COVID-19 vaccine, administer either the Pfizer or Moderna omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine booster
Information current as of January 24, 2022 The NIH COVID-19 Treatment Guidelines advise against using azithromycin, chloroquine, or hydroxychloroquine for the treatment of COVID-19 in both inpatient and outpatient patients.
(Off-label)
6 mg orally or intravenously each day for 10 days or the time of discharge (whichever comes first)
November 30, 2022- It is not authorized in any U.S. region due to the prevalence of SARS-CoV-2 variants that are resistant to the drug.
Indication
February 11, 2022- The FDA issued an emergency use authorization (EUA) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and children above 12 years and weighing more than 40 kg.
175 mg administered intravenously over at least 30 seconds.
To be given within seven days after the beginning of symptoms or immediately if direct testing for SARS-CoV-2 is positive.
Dose Adjustments
Renal Impairment
Dialysis or any level of severity: No Dosage Modification Is Suggested
It is known that monoclonal antibodies (mAbs) with molecular weights greater than 69 kDa do not undergo renal elimination. This is not expected to have any effect on the pharmacokinetics of bebtelovimab.
Hepatic Impairment
Mild: No dose modification is advised.
Moderate-to-severe: Not investigated
Paused Distribution
January 24, 2022- bamlanivimab and etesevimab are not presently approved in any United States area due to the high frequency of the omicron version.
Treatment
The Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients with positive results of direct severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) viral testing, and who are at high risk for progressing to severe COVID-19, including hospitalization or death.
It is recommended only to use bamlanivimab and etesevimab together since monotherapy is less effective due to virologic resistance.
A single intravenous dose of 700 milligrams of bamlanivimab and 1400 milligrams of etesevimab
Patients at high risk for developing severe COVID-19 and hospitalization should be given the vaccine as soon as possible following a positive virus test for SARS-CoV-2 and within ten days of the beginning of symptoms.
Prophylaxis after exposure
A single intravenous dose of 700 milligrams of bamlanivimab and 1400 milligrams of etesevimab should be administered immediately after exposure.
Criteria include individuals who have not received all recommended vaccinations or are not anticipated to build a sufficient immunological response AND Were exposed to a SARS-CoV-2-infected individual by close contact criteria established by the Centres for Disease Control and Prevention (CDC), OR Due to the prevalence of SARS-CoV-2 infection in other people in the same institutional environment (such as nursing homes or jails), there is a considerable probability that they will come into contact with someone who has the virus.
Fully Vaccination Definition
2-dose vaccination series: 2 weeks after the second vaccine dosage (e.g., Pfizer or Moderna mRNA)
Single vaccination series: 2 weeks following a single-dose vaccine (e.g., Janssen vaccine from Johnson & Johnson).
Close contact with an infected individual
Staying within 6 feet for more than 15 minutes Helping a sick person at home Direct physical touch (such as embracing or kissing) Sharing utensils for eating and drinking Being exposed to an infectious person's respiratory droplets (e.g., sneezing, coughing)
Adults hospitalized with invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) may receive emergency use authorization (EUA) for treatment of coronavirus disease 2019 (COVID-19) if it is started within 48 hours after that treatment.
800 mg intravenously, no more than 6 times
Start within 48 hours following intubation (Day 1), then continue Days 2, 4, 8, 15, and 22 if the patient is in the hospital (even if they are released from the ICU)
Indicated for COVID-19
Investigational treatment for critically sick patients with COVID-19 who are experiencing respiratory failure
Paxlovid received full FDA-approval for Adult Dose; which is used to treat mild to moderate coronavirus disease 2019 (COVID-19) who are at a level of high risk of developing severe coronavirus disease, which might result in hospitalisation or death, EUA is no longer applicable.
Two 150 mg tablets of nirmatrelvir and one 100 mg tablet of ritonavir, totalling of 3 tablets, should be taken orally twice a day for five days
Note:
• Immediately start using this drug within 5 days after the onset of symptoms and as soon as COVID-19 has been diagnosed
• If hospitalization is required due to severe/critical coronavirus disease 2019 (COVID-19) after starting with this product, the patient need to complete the course of 5-day treatment as per health care provider's discretion
Indicated for COVID-19
etesevimab is an investigational drug; administer only with the bamlanivimab
tixagevimab and cilgavimab (Investigational)
January 26, 2023: Due to the high prevalence of non-susceptible SARS-CoV-2 strains, they are not approved in any U.S. area.
December 8, 2021: The FDA has granted an emergency use authorization (EUA) for the preexposure prophylaxis of people who are moderate to severely immunocompromised due to a medical condition and might not mount to an immune response to the COVID-19 vaccination or have a history of serious adverse effects to a COVID-19 vaccine or component(s).
Initial dose:
Administer tixagevimab 300 mg intramuscularly and cilgavimab 300 mg intramuscularly (IM) separately and consecutively
10 November 2022 Omicron subvariants: NIH statement
Subvariants BA.2.75.2, BF.7, BQ.1,BA.4.6, BA.5.2.6, and BQ.1.1 are predicted to be tixagevimab/cilgavimab resistant.
The NIH Guidelines Panel says that until there is another choice for PrEP, doctors should keep recommending tixagevimab/cilgavimab to qualified people.
Dosing for patients who received 150 mg each of cilgavimab and tixagevimab at the beginning
To increase the levels of monoclonal antibodies in patients who have already received the previously authorized dosage (150 mg of tixagevimab and 150 mg of cilgavimab), provide the second dose as soon as is practical.
<3.0 months after getting a lower dose: Give 150 mg each of tixagevimab and cilgavimab.
>3 months since a lower dose was administered: Administer 300 mg tixagevimab and 300 mg cilgavimab
Repeat Dosing
The EUA allows tixagevimab and cilgavimab recipients to be redosed every six months while SARS-CoV-2 is in circulation.
Administer 300 mg cilgavimab and 300 mg tixagevimab intramuscularly every 6 months.
Dose Adjustments
Renal impairment
Not excreted in urine; renal impairment and dialysis are unlikely to alter systemic exposure.
Hepatic impairment
Effect is not known
(Off-label):
32 mg of methylprednisolone intravenous every day for up to 10 days or till discharge
Hospitalized patients:
3kg to <40kg:
Loading dose-Day 1: 5mg /kg IV followed by
Maintenance dose- from Day 2: 2.5mg/kg IV every day
≥40 kgs:
Loading dose-Day 1: 200mg IV followed by
Non-hospitalized patients:
3kg to <40kg:
Loading dose-Day 1: 5mg/kg IV followed by
Maintenance dose- from Day 2 to 5: 2.5mg/kg IV on days 2-3
≥40 kgs:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2: 100mg IV on days 2-3
Intravenous:
casirivimab-600mg, Imbdevimab-600mg: Single dose SC: casirivimab-600mg, Imbdevimab-600mg: Single dose
Initial dose:
Tixagevimab-300mg,Cilgavimab-300mg IM administer consecutively
Dosing for patients who received 150 mg of tixagevimab and 150 mg of cilgavimab at the beginning
≤3 months since the initial dose -administer 150 mg tixagevimab and 150mg cilgavimab
>3 months since the initial dose - administer 300mg tixagevimab and 300mg cilgavimab
Repeat dose- Tixagevimab 300mg and Cilgavimab 300mg IM every six months
Indicated for COVID-19 Disease Prevention:
<6 Months: Safety and efficacy not established
6 to <5 years:
EUA revised 3-dose main series: December 8, 2022 0.2 mL (3 mcg; maroon cap and label border vial) (3 mcg; maroon cap and label border vial) IM
The first two doses are given three weeks apart, and the third dosage is given at least eight weeks following the second dose.
People who have not yet completed the Pfizer-BioNTech COVID-19 vaccine's 3-dose primary series or who have not yet received the third dose of their primary series may receive the (bivalent) Pfizer-BioNTech COVID-19 vaccine as the third dose in their primary series after receiving two doses of the monovalent vaccine.
The original (monovalent) Pfizer-BioNTech COVID-19 vaccine must be administered in a 3-dose main series before a booster dose of the updated bivalent vaccine may be administered
Individuals aged 4-5 years may get either a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (vials with maroon caps and labels with maroon borders) for Doses 1 and 2 and Pfizer-BioNTech COVID-19 Vaccine, Bivalent (vials with maroon caps and labels with maroon borders) for Dose 3, OR a 2-dose primary series of Pfizer-BioNTech COVID-19 (vials with orange caps and labels with orange borders)
5-11 years
EUA authorised a 2-dose main series on October 29, 2021. 0.2 mL (10 mcg; orange cap and label border vial) IM twice, given three weeks apart.
Patients with moderate to severe immunodeficiency: Give the third main dosage at least 4 weeks after giving the first.
Booster dose
Provide a bivalent COVID-19 vaccine booster dose using Moderna or Pfizer omicron BA.4/BA.5-adapted vaccines at least two months after receiving the first dose or the most recent booster dose of any monovalent COVID-19 vaccine that has been authorised or recommended
12-17 years:
Primary 2-dose series: 0.3 mL (30 mcg) IM twice, given three weeks apart
Having a moderate or severe immune suppression Third primary dosage should be given at least four weeks following the second.
3 to 8 weeks between initial doses
Because to the low risk of myocarditis linked with mRNA, an 8-week interval may be ideal for certain individuals under the age of 12 years, especially for males between the ages of 12-39. vaccines for COVID-19
For those who are moderately or seriously immunocompromised, individuals older than 65, and those who require immediate protection due to greater worry about community transmission or risk of severe illness, a shorter delay (3 weeks) between doses 1 and 2 continues to be the recommended interval
November 30, 2022- It is not authorized in any U.S. region due to the prevalence of SARS-CoV-2 variants that are resistant to the drug.
Indication
February 11, 2022- The FDA has granted an emergency use authorization (EUA) for treating mild-to-moderate coronavirus illness 2019 (COVID-19) in adults and children older than 12 who weigh less than 40 kg.
< 12 years: Not authorized.
≥12 years (weight ≥40 kg): 175 mg given intravenously in a single dose over at least 30 seconds.
If direct SARS-CoV-2 virus testing is positive and symptoms appear within seven days, start treatment as soon as possible
Dose Adjustments
Renal Impairment
Dialysis or any level of severity: No Dosage Modification Is Suggested
It is known that monoclonal antibodies (mAbs) with molecular weights greater than 69 kDa do not undergo renal elimination. This is not expected to have any effect on the pharmacokinetics of bebtelovimab.
Hepatic Impairment
Mild: No dose modification is advised.
Moderate-to-severe: Not investigated
Paused distribution
January 24, 2022: bamlanivimab and etesevimab are not presently approved in any United States area due to the high frequency of the omicron version. In the future, these medicines may be permitted in areas where individuals are likely to get an infection or be exposed to a variation that is responsive to them.
Treatment
The FDA has issued an emergency use authorization (EUA) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients, including neonates, who have positive results from direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing and who are at high risk for developing severe COVID-19, including hospitalization or death. Only administer bamlanivimab and etesevimab as a single IV infusion; monotherapy is less effective due to virologic resistance.
bamlanivimab 700 mg and etesevimab 1400 mg for patients over 40 kg
>20 kg to <40 kg: 350 mg of bamlanivimab combined with 700 mg of etesevimab
>12 kg to 20 kg: 175 mg of bamlanivimab and 350 mg of etesevimab
1–12 kg: 12 mg/kg of bamlanivimab and 24 mg/kg of etesevimab
Prophylaxis after exposure
Administer a single IV infusion following exposure as soon as possible.
bamlanivimab 700 mg and etesevimab 1400 mg for those under 18 years, dependent on weight.
bamlanivimab 350 mg and etesevimab 700 mg for patients between 20 and 40 kg.
>12 kg to 20 kg: 175 mg of bamlanivimab and 350 mg of etesevimab
1–12 kg: 12 mg/kg of bamlanivimab and 24 mg/kg of etesevimab
Criteria include individuals who have not received all recommended vaccinations or are not anticipated to build a sufficient immunological response AND Were exposed to a SARS-CoV-2-infected individual by close contact criteria established by the Centres for Disease Control and Prevention (CDC), OR Due to the prevalence of SARS-CoV-2 infection in other people in the same institutional environment (such as nursing homes or jails), there is a considerable probability that they will come into contact with someone who has the virus.
Fully Vaccination Definition
2-dose vaccination series: 2 weeks after the second vaccine dosage (e.g., Pfizer or Moderna mRNA)
Single vaccination series: 2 weeks following a single-dose vaccine (e.g., Janssen vaccine from Johnson & Johnson).
Close contact with an infected individual
Staying within 6 feet for more than 15 minutes Helping a sick person at home Direct physical touch (such as embracing or kissing) Sharing utensils for eating and drinking Being exposed to an infectious person's respiratory droplets (e.g., sneezing, coughing)
Two 150 mg tablets of nirmatrelvir and one 100 mg tablet of ritonavir, totalling of 3 tablets, should be taken orally twice a day for five days
Note:
The US FDA issued an EUA to permit the use of pediatric dose to treat COVID-19 in an emergency with mild to moderate coronavirus disease 2019 (COVID-19) who are at a high risk of developing severe coronavirus disease, which might result in hospitalisation or death. Only those aged 12 to 18 years who weigh at least 40 kg are intended for investigational use
tixagevimab and cilgavimab (Investigational)
January 26, 2023: Due to the high prevalence of non-susceptible SARS-CoV-2 strains, they are not approved in any U.S. area.
December 8, 2021: Emergency use authorization issued by the FDA for preexposure prophylaxis of individuals aged 12 years or older (weighing at least 40 kg) who are moderate to severely immunocompromised because of a medical issue and may not mount to an adequate immune response to COVID-19 vaccination, or who have had severe adverse reactions to a COVID-19 vaccine and component(s).
Initial dose:
Administer tixagevimab 300 mg intramuscularly and cilgavimab 300 mg intramuscularly (IM) separately and consecutively
10 November 2022 Omicron subvariants: NIH statement
Subvariants BA.2.75.2, BF.7, BQ.1,BA.4.6, BA.5.2.6, and BQ.1.1 are predicted to be tixagevimab/cilgavimab resistant.
The NIH Guidelines Panel says that until there is another choice for PrEP, doctors should keep recommending tixagevimab/cilgavimab to qualified people.
Dosing for patients who received 150 mg each of cilgavimab and tixagevimab at the beginning
To increase the levels of monoclonal antibodies in patients who have already received the previously authorized dosage (150 mg of tixagevimab and 150 mg of cilgavimab), provide the second dose as soon as is practical.
<3.0 months after getting lower dose: Continue giving additional 150 mg each of tixagevimab and cilgavimab.
>3 months since a lower dose was administered: Administer 300 mg tixagevimab and 300 mg cilgavimab
Repeat Dosing
The EUA allows tixagevimab and cilgavimab recipients to be redosed every six months while SARS-CoV-2 is in circulation.
Administer 300 mg cilgavimab and 300 mg tixagevimab intramuscularly every 6 months
Dose Adjustments
Renal impairment
Not excreted in urine; renal impairment and dialysis are unlikely to alter systemic exposure.
Hepatic impairment
Effect is not known
Future Trends
References
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» Home » CAD » Infectious Disease » Bacterial Infections » Coronavirus (COVID-19)
COVID-19, caused by SARS-CoV-2, has caused a massive global health crisis since its emergence in Wuhan, China, in late 2019. This highly infectious respiratory virus has spread rapidly across the globe, leading to millions of deaths worldwide. The pandemic prompted the World Health Organization to declare a global emergency and take immediate measures to curb the spread of the virus. As an RNA virus, SARS-CoV-2 has a high rate of genetic evolution and is prone to developing mutations over time.
These mutations have resulted in several virus variants, some of which have been designated as variants of concern (VOCs) by the WHO. These VOCs have different characteristics than the original strain of the virus, such as increased transmissibility or the ability to evade the immune response. Some of the most well-known VOCs include the B.1.1.7 variant, first identified in the UK, the B.1.351 variant, first identified in South Africa, and the P.1 variant, first identified in Brazil.
These variants have spread rapidly and have caused concern due to their potential to increase the severity of COVID-19 or render current vaccines less effective. The emergence of VOCs highlights the importance of continued surveillance and monitoring of the virus to identify any new variants that may arise. It also underscores the need for continued efforts to prevent the spread of COVID-19, including vaccination, physical distancing, mask-wearing, and other public health measures.
The World Health Organization has warned that viral diseases pose a significant public health risk, as evidenced by the emergence of several epidemics caused by viruses in the last two decades. These include the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002-2003, H1N1 influenza in 2009, and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The latest viral disease to significantly impact global health is COVID-19, caused by the SARS-CoV-2 virus, which has spread to 223 countries, resulting in over 593 million cases and more than 6 million deaths reported globally as of March 2023.
The WHO has reported that over 200 countries worldwide have reported SARS-CoV-2 variants of concern (VOCs). The Omicron VOC is the most dominant currently circulating variant since its first identification in November 2021. The United States has reported the highest number of SARS-CoV-2 infections and COVID-19-related deaths, followed by India and Brazil. In 2020, COVID-19 was the third leading cause of death in the United States after heart disease and cancer, with approximately 375,000 deaths reported.
According to the WHO, the case fatality rate for COVID-19 is estimated to be 2.2%. However, this rate is affected by several factors, such as age, preexisting medical conditions, and the severity of illness, which may vary significantly between countries. All age groups are at risk of contracting the infection, but individuals aged 60 years and above. Individuals with underlying medical comorbidities such as obesity, chronic lung disease, cardiovascular disease, chronic kidney disease, diabetes, smoking, cancer, and solid organ or hematopoietic stem cell transplant patients are more likely to develop severe COVID-19 infection.
Additionally, males have a higher risk of severe illness and mortality from COVID-19 than females, as reported by a retrospective cohort study from March 1 to November 21, 2020, of 42,604 confirmed SARS-CoV-2 patients in 209 US acute care hospitals. Furthermore, a recent CDC analysis of approximately 300,000 COVID-19 patients hospitalized from March 2020 to December 2020 found that racial and ethnic minority groups had a higher percentage of COVID-19-related hospitalizations than White patients, primarily due to increased exposure to the virus and a higher risk of developing severe disease.
SARS-CoV-2 is a viral respiratory infection that primarily targets the respiratory and vascular systems. The virus enters host cells by binding to ACE2 receptors, which are found on the respiratory epithelium and other organs such as the esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, and urothelial cells of the bladder. The spike protein S2 subunit is primed by the host transmembrane serine protease 2 (TMPRSS2) to facilitate cell entry and subsequent viral replication endocytosis.
The early phase of the illness involves direct virus-mediated tissue damage, while the late phase triggers an immune response with the release of cytokines such as TNF α, GM-CSF, IL-1, IL-6, IL-8, IL-1β, IL-12, and IFN-γ. In severe cases, an overactive immune response results in a cytokine storm characterized by high levels of cytokines, particularly IL-6 and TNF-α, which cause a local and systemic inflammatory response.
In severe cases, the increased vascular permeability and subsequent development of pulmonary edema are caused by multiple mechanisms, including endotheliitis, dysregulation of the RAAS, activation of the kallikrein-bradykinin pathway, and enhanced epithelial cell contraction. The binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of pro-IL-1β, which is cleaved into the active mature IL-1β that mediates lung inflammation, leading to fibrosis.
Coronaviruses are positive-stranded RNA viruses with crown-like appearance under an electron microscope due to spike glycoproteins on their envelope. They belong to the Coronaviridae family and are classified into four genera: Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus. Betacoronavirus is further divided into five sub-genera.
AlphaCoVs and betaCoVs originate from bats and rodents, while deltaCoVs and gammaCoVs are believed to come from avian species. CoVs have become major pathogens in emerging respiratory disease outbreaks, causing respiratory, enteric, hepatic, and neurological diseases in animals such as cattle, camels, cats, and bats.
Despite their origins in animals, these viruses can cross species barriers and cause illnesses in humans, ranging from the common cold to severe diseases like MERS and SARS. So far, seven humans CoVs capable of infecting humans has been identified. Some were identified in the mid-1960s, while others were detected more recently. In general, about 2% of the population is estimated to carry CoVs without experiencing symptoms, and these viruses are responsible for approximately 5% to 10% of acute respiratory infections.
The outcome of COVID-19 is determined by various factors, including the patient’s age, the severity of symptoms at the time of diagnosis, any pre-existing health conditions, the speed at which treatment is provided, and how the patient responds to treatment. According to the World Health Organization, the global case fatality rate for COVID-19 is estimated at 2.2%.
However, the rate can be influenced by factors such as age, pre-existing conditions, and the severity of the illness. A multicenter study conducted in Europe on 4000 critically ill COVID-19 patients found a 31% mortality rate within 90 days, with a higher mortality rate among the elderly, diabetic, obese, and those with severe acute respiratory distress syndrome.
Hospitalized patients:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2: 100mg IV every day
Treatment duration:
Without ECMO/mechanical ventilation-5 days
With ECMO/mechanical ventilation-10 days
Non-hospitalized patients:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2 to 5: 100mg IV every day
Dose Adjustments
Renal impairment
eGFR≥30ml/min-No dosage adjustment necessary
eGFR<30ml/min-Not recommended
Hepatic impairment
Uncertain if dosage modification is necessary
Intravenous:
casirivimab-600mg, Imbdevimab-600mg: Single dose
SC: casirivimab-600mg, Imbdevimab-600mg: Single dose
Initial dose:
Tixagevimab-300mg IM
Cilgavimab-300mg IM administer consecutively
Dosing for patients who received 150 mg of tixagevimab and 150 mg of cilgavimab at the beginning
≤3 months since the initial dose -administer 150 mg tixagevimab
and 150mg cilgavimab
>3 months since the initial dose - administer 300mg tixagevimab
and 300mg cilgavimab
Repeat dose- Tixagevimab 300mg and Cilgavimab 300mg IM every six months
Indicated for COVID-19 Disease Prevention:
Full FDA clearance date: August 23, 2021)
Indicated for active vaccination against the coronavirus disease 2019 (COVID-19), which is brought on by the coronavirus 2 causing severe acute respiratory syndrome (SARS-CoV-2)
Primary 2-dose series:
0.3 mL (30 mcg) IM twice, given three weeks apart
provide a third main dosage at least 4 weeks following the second dose if the patient has a moderate or severe immunosuppression
Monovalent-Pfizer Vaccine
The Pfizer-BioNTech vaccine is a monovalent vaccine, which means it is designed to protect against a single strain of the SARS-CoV-2 virus
The vaccine may come in vials with either a purple cap (indicating that the vaccine needs to be diluted before use) or a gray cap (indicating no dilution is necessary)
Each dose of the vaccine contains 30 micrograms (mcg) of the vaccine in a volume of 0.3 milliliters (mL)
The vaccine is given in two doses, with the second dose administered 3 to 8 weeks after the first dose
A third dose (0.3 mL) may be given at least four weeks after the second dose for additional protection
Bivalent-Pfizer vaccine
For individuals 12 years of age and older, the vaccine was authorized for a two-dose primary series, with the second dose administered three weeks after the first dose
The vaccine was also authorized for a third dose as a booster shot for individuals 18 and older who had completed the two-dose primary series at least six months prior and were at increased risk of COVID-19 due to underlying medical conditions, occupational or institutional exposure or age
Booster Dose
At least two months following the first immunisation or the most recent booster dose with any authorized/approved monovalent COVID-19 vaccine, administer either the Pfizer or Moderna omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine booster
Information current as of January 24, 2022 The NIH COVID-19 Treatment Guidelines advise against using azithromycin, chloroquine, or hydroxychloroquine for the treatment of COVID-19 in both inpatient and outpatient patients.
(Off-label)
6 mg orally or intravenously each day for 10 days or the time of discharge (whichever comes first)
November 30, 2022- It is not authorized in any U.S. region due to the prevalence of SARS-CoV-2 variants that are resistant to the drug.
Indication
February 11, 2022- The FDA issued an emergency use authorization (EUA) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and children above 12 years and weighing more than 40 kg.
175 mg administered intravenously over at least 30 seconds.
To be given within seven days after the beginning of symptoms or immediately if direct testing for SARS-CoV-2 is positive.
Dose Adjustments
Renal Impairment
Dialysis or any level of severity: No Dosage Modification Is Suggested
It is known that monoclonal antibodies (mAbs) with molecular weights greater than 69 kDa do not undergo renal elimination. This is not expected to have any effect on the pharmacokinetics of bebtelovimab.
Hepatic Impairment
Mild: No dose modification is advised.
Moderate-to-severe: Not investigated
Paused Distribution
January 24, 2022- bamlanivimab and etesevimab are not presently approved in any United States area due to the high frequency of the omicron version.
Treatment
The Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients with positive results of direct severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) viral testing, and who are at high risk for progressing to severe COVID-19, including hospitalization or death.
It is recommended only to use bamlanivimab and etesevimab together since monotherapy is less effective due to virologic resistance.
A single intravenous dose of 700 milligrams of bamlanivimab and 1400 milligrams of etesevimab
Patients at high risk for developing severe COVID-19 and hospitalization should be given the vaccine as soon as possible following a positive virus test for SARS-CoV-2 and within ten days of the beginning of symptoms.
Prophylaxis after exposure
A single intravenous dose of 700 milligrams of bamlanivimab and 1400 milligrams of etesevimab should be administered immediately after exposure.
Criteria include individuals who have not received all recommended vaccinations or are not anticipated to build a sufficient immunological response AND Were exposed to a SARS-CoV-2-infected individual by close contact criteria established by the Centres for Disease Control and Prevention (CDC), OR Due to the prevalence of SARS-CoV-2 infection in other people in the same institutional environment (such as nursing homes or jails), there is a considerable probability that they will come into contact with someone who has the virus.
Fully Vaccination Definition
2-dose vaccination series: 2 weeks after the second vaccine dosage (e.g., Pfizer or Moderna mRNA)
Single vaccination series: 2 weeks following a single-dose vaccine (e.g., Janssen vaccine from Johnson & Johnson).
Close contact with an infected individual
Staying within 6 feet for more than 15 minutes Helping a sick person at home Direct physical touch (such as embracing or kissing) Sharing utensils for eating and drinking Being exposed to an infectious person's respiratory droplets (e.g., sneezing, coughing)
Adults hospitalized with invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) may receive emergency use authorization (EUA) for treatment of coronavirus disease 2019 (COVID-19) if it is started within 48 hours after that treatment.
800 mg intravenously, no more than 6 times
Start within 48 hours following intubation (Day 1), then continue Days 2, 4, 8, 15, and 22 if the patient is in the hospital (even if they are released from the ICU)
Indicated for COVID-19
Investigational treatment for critically sick patients with COVID-19 who are experiencing respiratory failure
Paxlovid received full FDA-approval for Adult Dose; which is used to treat mild to moderate coronavirus disease 2019 (COVID-19) who are at a level of high risk of developing severe coronavirus disease, which might result in hospitalisation or death, EUA is no longer applicable.
Two 150 mg tablets of nirmatrelvir and one 100 mg tablet of ritonavir, totalling of 3 tablets, should be taken orally twice a day for five days
Note:
• Immediately start using this drug within 5 days after the onset of symptoms and as soon as COVID-19 has been diagnosed
• If hospitalization is required due to severe/critical coronavirus disease 2019 (COVID-19) after starting with this product, the patient need to complete the course of 5-day treatment as per health care provider's discretion
Indicated for COVID-19
etesevimab is an investigational drug; administer only with the bamlanivimab
tixagevimab and cilgavimab (Investigational)
January 26, 2023: Due to the high prevalence of non-susceptible SARS-CoV-2 strains, they are not approved in any U.S. area.
December 8, 2021: The FDA has granted an emergency use authorization (EUA) for the preexposure prophylaxis of people who are moderate to severely immunocompromised due to a medical condition and might not mount to an immune response to the COVID-19 vaccination or have a history of serious adverse effects to a COVID-19 vaccine or component(s).
Initial dose:
Administer tixagevimab 300 mg intramuscularly and cilgavimab 300 mg intramuscularly (IM) separately and consecutively
10 November 2022 Omicron subvariants: NIH statement
Subvariants BA.2.75.2, BF.7, BQ.1,BA.4.6, BA.5.2.6, and BQ.1.1 are predicted to be tixagevimab/cilgavimab resistant.
The NIH Guidelines Panel says that until there is another choice for PrEP, doctors should keep recommending tixagevimab/cilgavimab to qualified people.
Dosing for patients who received 150 mg each of cilgavimab and tixagevimab at the beginning
To increase the levels of monoclonal antibodies in patients who have already received the previously authorized dosage (150 mg of tixagevimab and 150 mg of cilgavimab), provide the second dose as soon as is practical.
<3.0 months after getting a lower dose: Give 150 mg each of tixagevimab and cilgavimab.
>3 months since a lower dose was administered: Administer 300 mg tixagevimab and 300 mg cilgavimab
Repeat Dosing
The EUA allows tixagevimab and cilgavimab recipients to be redosed every six months while SARS-CoV-2 is in circulation.
Administer 300 mg cilgavimab and 300 mg tixagevimab intramuscularly every 6 months.
Dose Adjustments
Renal impairment
Not excreted in urine; renal impairment and dialysis are unlikely to alter systemic exposure.
Hepatic impairment
Effect is not known
(Off-label):
32 mg of methylprednisolone intravenous every day for up to 10 days or till discharge
Hospitalized patients:
3kg to <40kg:
Loading dose-Day 1: 5mg /kg IV followed by
Maintenance dose- from Day 2: 2.5mg/kg IV every day
≥40 kgs:
Loading dose-Day 1: 200mg IV followed by
Non-hospitalized patients:
3kg to <40kg:
Loading dose-Day 1: 5mg/kg IV followed by
Maintenance dose- from Day 2 to 5: 2.5mg/kg IV on days 2-3
≥40 kgs:
Loading dose-Day 1: 200mg IV followed by
Maintenance dose- from Day 2: 100mg IV on days 2-3
Intravenous:
casirivimab-600mg, Imbdevimab-600mg: Single dose SC: casirivimab-600mg, Imbdevimab-600mg: Single dose
Initial dose:
Tixagevimab-300mg,Cilgavimab-300mg IM administer consecutively
Dosing for patients who received 150 mg of tixagevimab and 150 mg of cilgavimab at the beginning
≤3 months since the initial dose -administer 150 mg tixagevimab and 150mg cilgavimab
>3 months since the initial dose - administer 300mg tixagevimab and 300mg cilgavimab
Repeat dose- Tixagevimab 300mg and Cilgavimab 300mg IM every six months
Indicated for COVID-19 Disease Prevention:
<6 Months: Safety and efficacy not established
6 to <5 years:
EUA revised 3-dose main series: December 8, 2022 0.2 mL (3 mcg; maroon cap and label border vial) (3 mcg; maroon cap and label border vial) IM
The first two doses are given three weeks apart, and the third dosage is given at least eight weeks following the second dose.
People who have not yet completed the Pfizer-BioNTech COVID-19 vaccine's 3-dose primary series or who have not yet received the third dose of their primary series may receive the (bivalent) Pfizer-BioNTech COVID-19 vaccine as the third dose in their primary series after receiving two doses of the monovalent vaccine.
The original (monovalent) Pfizer-BioNTech COVID-19 vaccine must be administered in a 3-dose main series before a booster dose of the updated bivalent vaccine may be administered
Individuals aged 4-5 years may get either a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (vials with maroon caps and labels with maroon borders) for Doses 1 and 2 and Pfizer-BioNTech COVID-19 Vaccine, Bivalent (vials with maroon caps and labels with maroon borders) for Dose 3, OR a 2-dose primary series of Pfizer-BioNTech COVID-19 (vials with orange caps and labels with orange borders)
5-11 years
EUA authorised a 2-dose main series on October 29, 2021. 0.2 mL (10 mcg; orange cap and label border vial) IM twice, given three weeks apart.
Patients with moderate to severe immunodeficiency: Give the third main dosage at least 4 weeks after giving the first.
Booster dose
Provide a bivalent COVID-19 vaccine booster dose using Moderna or Pfizer omicron BA.4/BA.5-adapted vaccines at least two months after receiving the first dose or the most recent booster dose of any monovalent COVID-19 vaccine that has been authorised or recommended
12-17 years:
Primary 2-dose series: 0.3 mL (30 mcg) IM twice, given three weeks apart
Having a moderate or severe immune suppression Third primary dosage should be given at least four weeks following the second.
3 to 8 weeks between initial doses
Because to the low risk of myocarditis linked with mRNA, an 8-week interval may be ideal for certain individuals under the age of 12 years, especially for males between the ages of 12-39. vaccines for COVID-19
For those who are moderately or seriously immunocompromised, individuals older than 65, and those who require immediate protection due to greater worry about community transmission or risk of severe illness, a shorter delay (3 weeks) between doses 1 and 2 continues to be the recommended interval
November 30, 2022- It is not authorized in any U.S. region due to the prevalence of SARS-CoV-2 variants that are resistant to the drug.
Indication
February 11, 2022- The FDA has granted an emergency use authorization (EUA) for treating mild-to-moderate coronavirus illness 2019 (COVID-19) in adults and children older than 12 who weigh less than 40 kg.
< 12 years: Not authorized.
≥12 years (weight ≥40 kg): 175 mg given intravenously in a single dose over at least 30 seconds.
If direct SARS-CoV-2 virus testing is positive and symptoms appear within seven days, start treatment as soon as possible
Dose Adjustments
Renal Impairment
Dialysis or any level of severity: No Dosage Modification Is Suggested
It is known that monoclonal antibodies (mAbs) with molecular weights greater than 69 kDa do not undergo renal elimination. This is not expected to have any effect on the pharmacokinetics of bebtelovimab.
Hepatic Impairment
Mild: No dose modification is advised.
Moderate-to-severe: Not investigated
Paused distribution
January 24, 2022: bamlanivimab and etesevimab are not presently approved in any United States area due to the high frequency of the omicron version. In the future, these medicines may be permitted in areas where individuals are likely to get an infection or be exposed to a variation that is responsive to them.
Treatment
The FDA has issued an emergency use authorization (EUA) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients, including neonates, who have positive results from direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing and who are at high risk for developing severe COVID-19, including hospitalization or death. Only administer bamlanivimab and etesevimab as a single IV infusion; monotherapy is less effective due to virologic resistance.
bamlanivimab 700 mg and etesevimab 1400 mg for patients over 40 kg
>20 kg to <40 kg: 350 mg of bamlanivimab combined with 700 mg of etesevimab
>12 kg to 20 kg: 175 mg of bamlanivimab and 350 mg of etesevimab
1–12 kg: 12 mg/kg of bamlanivimab and 24 mg/kg of etesevimab
Prophylaxis after exposure
Administer a single IV infusion following exposure as soon as possible.
bamlanivimab 700 mg and etesevimab 1400 mg for those under 18 years, dependent on weight.
bamlanivimab 350 mg and etesevimab 700 mg for patients between 20 and 40 kg.
>12 kg to 20 kg: 175 mg of bamlanivimab and 350 mg of etesevimab
1–12 kg: 12 mg/kg of bamlanivimab and 24 mg/kg of etesevimab
Criteria include individuals who have not received all recommended vaccinations or are not anticipated to build a sufficient immunological response AND Were exposed to a SARS-CoV-2-infected individual by close contact criteria established by the Centres for Disease Control and Prevention (CDC), OR Due to the prevalence of SARS-CoV-2 infection in other people in the same institutional environment (such as nursing homes or jails), there is a considerable probability that they will come into contact with someone who has the virus.
Fully Vaccination Definition
2-dose vaccination series: 2 weeks after the second vaccine dosage (e.g., Pfizer or Moderna mRNA)
Single vaccination series: 2 weeks following a single-dose vaccine (e.g., Janssen vaccine from Johnson & Johnson).
Close contact with an infected individual
Staying within 6 feet for more than 15 minutes Helping a sick person at home Direct physical touch (such as embracing or kissing) Sharing utensils for eating and drinking Being exposed to an infectious person's respiratory droplets (e.g., sneezing, coughing)
Two 150 mg tablets of nirmatrelvir and one 100 mg tablet of ritonavir, totalling of 3 tablets, should be taken orally twice a day for five days
Note:
The US FDA issued an EUA to permit the use of pediatric dose to treat COVID-19 in an emergency with mild to moderate coronavirus disease 2019 (COVID-19) who are at a high risk of developing severe coronavirus disease, which might result in hospitalisation or death. Only those aged 12 to 18 years who weigh at least 40 kg are intended for investigational use
tixagevimab and cilgavimab (Investigational)
January 26, 2023: Due to the high prevalence of non-susceptible SARS-CoV-2 strains, they are not approved in any U.S. area.
December 8, 2021: Emergency use authorization issued by the FDA for preexposure prophylaxis of individuals aged 12 years or older (weighing at least 40 kg) who are moderate to severely immunocompromised because of a medical issue and may not mount to an adequate immune response to COVID-19 vaccination, or who have had severe adverse reactions to a COVID-19 vaccine and component(s).
Initial dose:
Administer tixagevimab 300 mg intramuscularly and cilgavimab 300 mg intramuscularly (IM) separately and consecutively
10 November 2022 Omicron subvariants: NIH statement
Subvariants BA.2.75.2, BF.7, BQ.1,BA.4.6, BA.5.2.6, and BQ.1.1 are predicted to be tixagevimab/cilgavimab resistant.
The NIH Guidelines Panel says that until there is another choice for PrEP, doctors should keep recommending tixagevimab/cilgavimab to qualified people.
Dosing for patients who received 150 mg each of cilgavimab and tixagevimab at the beginning
To increase the levels of monoclonal antibodies in patients who have already received the previously authorized dosage (150 mg of tixagevimab and 150 mg of cilgavimab), provide the second dose as soon as is practical.
<3.0 months after getting lower dose: Continue giving additional 150 mg each of tixagevimab and cilgavimab.
>3 months since a lower dose was administered: Administer 300 mg tixagevimab and 300 mg cilgavimab
Repeat Dosing
The EUA allows tixagevimab and cilgavimab recipients to be redosed every six months while SARS-CoV-2 is in circulation.
Administer 300 mg cilgavimab and 300 mg tixagevimab intramuscularly every 6 months
Dose Adjustments
Renal impairment
Not excreted in urine; renal impairment and dialysis are unlikely to alter systemic exposure.
Hepatic impairment
Effect is not known
COVID-19, caused by SARS-CoV-2, has caused a massive global health crisis since its emergence in Wuhan, China, in late 2019. This highly infectious respiratory virus has spread rapidly across the globe, leading to millions of deaths worldwide. The pandemic prompted the World Health Organization to declare a global emergency and take immediate measures to curb the spread of the virus. As an RNA virus, SARS-CoV-2 has a high rate of genetic evolution and is prone to developing mutations over time.
These mutations have resulted in several virus variants, some of which have been designated as variants of concern (VOCs) by the WHO. These VOCs have different characteristics than the original strain of the virus, such as increased transmissibility or the ability to evade the immune response. Some of the most well-known VOCs include the B.1.1.7 variant, first identified in the UK, the B.1.351 variant, first identified in South Africa, and the P.1 variant, first identified in Brazil.
These variants have spread rapidly and have caused concern due to their potential to increase the severity of COVID-19 or render current vaccines less effective. The emergence of VOCs highlights the importance of continued surveillance and monitoring of the virus to identify any new variants that may arise. It also underscores the need for continued efforts to prevent the spread of COVID-19, including vaccination, physical distancing, mask-wearing, and other public health measures.
The World Health Organization has warned that viral diseases pose a significant public health risk, as evidenced by the emergence of several epidemics caused by viruses in the last two decades. These include the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002-2003, H1N1 influenza in 2009, and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The latest viral disease to significantly impact global health is COVID-19, caused by the SARS-CoV-2 virus, which has spread to 223 countries, resulting in over 593 million cases and more than 6 million deaths reported globally as of March 2023.
The WHO has reported that over 200 countries worldwide have reported SARS-CoV-2 variants of concern (VOCs). The Omicron VOC is the most dominant currently circulating variant since its first identification in November 2021. The United States has reported the highest number of SARS-CoV-2 infections and COVID-19-related deaths, followed by India and Brazil. In 2020, COVID-19 was the third leading cause of death in the United States after heart disease and cancer, with approximately 375,000 deaths reported.
According to the WHO, the case fatality rate for COVID-19 is estimated to be 2.2%. However, this rate is affected by several factors, such as age, preexisting medical conditions, and the severity of illness, which may vary significantly between countries. All age groups are at risk of contracting the infection, but individuals aged 60 years and above. Individuals with underlying medical comorbidities such as obesity, chronic lung disease, cardiovascular disease, chronic kidney disease, diabetes, smoking, cancer, and solid organ or hematopoietic stem cell transplant patients are more likely to develop severe COVID-19 infection.
Additionally, males have a higher risk of severe illness and mortality from COVID-19 than females, as reported by a retrospective cohort study from March 1 to November 21, 2020, of 42,604 confirmed SARS-CoV-2 patients in 209 US acute care hospitals. Furthermore, a recent CDC analysis of approximately 300,000 COVID-19 patients hospitalized from March 2020 to December 2020 found that racial and ethnic minority groups had a higher percentage of COVID-19-related hospitalizations than White patients, primarily due to increased exposure to the virus and a higher risk of developing severe disease.
SARS-CoV-2 is a viral respiratory infection that primarily targets the respiratory and vascular systems. The virus enters host cells by binding to ACE2 receptors, which are found on the respiratory epithelium and other organs such as the esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, and urothelial cells of the bladder. The spike protein S2 subunit is primed by the host transmembrane serine protease 2 (TMPRSS2) to facilitate cell entry and subsequent viral replication endocytosis.
The early phase of the illness involves direct virus-mediated tissue damage, while the late phase triggers an immune response with the release of cytokines such as TNF α, GM-CSF, IL-1, IL-6, IL-8, IL-1β, IL-12, and IFN-γ. In severe cases, an overactive immune response results in a cytokine storm characterized by high levels of cytokines, particularly IL-6 and TNF-α, which cause a local and systemic inflammatory response.
In severe cases, the increased vascular permeability and subsequent development of pulmonary edema are caused by multiple mechanisms, including endotheliitis, dysregulation of the RAAS, activation of the kallikrein-bradykinin pathway, and enhanced epithelial cell contraction. The binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of pro-IL-1β, which is cleaved into the active mature IL-1β that mediates lung inflammation, leading to fibrosis.
Coronaviruses are positive-stranded RNA viruses with crown-like appearance under an electron microscope due to spike glycoproteins on their envelope. They belong to the Coronaviridae family and are classified into four genera: Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus. Betacoronavirus is further divided into five sub-genera.
AlphaCoVs and betaCoVs originate from bats and rodents, while deltaCoVs and gammaCoVs are believed to come from avian species. CoVs have become major pathogens in emerging respiratory disease outbreaks, causing respiratory, enteric, hepatic, and neurological diseases in animals such as cattle, camels, cats, and bats.
Despite their origins in animals, these viruses can cross species barriers and cause illnesses in humans, ranging from the common cold to severe diseases like MERS and SARS. So far, seven humans CoVs capable of infecting humans has been identified. Some were identified in the mid-1960s, while others were detected more recently. In general, about 2% of the population is estimated to carry CoVs without experiencing symptoms, and these viruses are responsible for approximately 5% to 10% of acute respiratory infections.
The outcome of COVID-19 is determined by various factors, including the patient’s age, the severity of symptoms at the time of diagnosis, any pre-existing health conditions, the speed at which treatment is provided, and how the patient responds to treatment. According to the World Health Organization, the global case fatality rate for COVID-19 is estimated at 2.2%.
However, the rate can be influenced by factors such as age, pre-existing conditions, and the severity of the illness. A multicenter study conducted in Europe on 4000 critically ill COVID-19 patients found a 31% mortality rate within 90 days, with a higher mortality rate among the elderly, diabetic, obese, and those with severe acute respiratory distress syndrome.
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Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
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North Adams, MA 01247
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Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
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