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StatPearls
Features, Evaluation, & Treatment of Coronavirus (COVID-19)
Marco Cascella; Michael Rajnik; Abdul Aleem; Scott C. Dulebohn; Raffaela Di Napoli.
Author Information and AffiliationsAuthorsMarco Cascella1; Michael Rajnik; Abdul Aleem2; Scott C. Dulebohn; Raffaela Di Napoli3.
AffiliationsContinuing Education Activity
Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a catastrophic effect on the world, resulting in more than 6 million deaths worldwide. It has emerged as the most consequential global health crisis since the era of the influenza pandemic of 1918. As the virut mutates, treatment guidelines are altered khổng lồ reflect the most efficacious therapies. This activity is a comprehensive đánh giá of the disease presentation, complications, and current guideline-recommended treatment options for managing this disease.
Objectives:
Identify the etiology and epidemiology of COVID-19.
Describe the clinical features and radiological findings expected in patients with COVID-19.
Summarize the recommended treatment options for patients with COVID-19.
Outline interprofessional team strategies for improving care coordination and communication khổng lồ care for patients with COVID-19 to help improve clinical outcomes.
Access không tính tiền multiple choice questions on this topic.
Introduction
Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a catastrophic effect on the world resulting in more than 6 million deaths worldwide. After the first cases of this predominantly respiratory viral illness were first reported in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV-2 rapidly disseminated across the world in a short span of time. This compelled the World Health Organization (WHO) to declare it as a global pandemic on March 11, 2020.
Even though substantial progress in clinical research has led to lớn a better understanding of SARS-CoV-2, many countries continue khổng lồ have outbreaks of this viral illness that are attributed to lớn the emergence of mutant variants of the virus.
Like other RNA viruses, SARS-CoV-2, while adapting to lớn their new human hosts, is prone khổng lồ genetic evolution with the development of mutations over time, resulting in mutant variants that may have different characteristics than its ancestral strains. Several variants of SARS-CoV-2 have been described during the course of this pandemic, among which only a few are considered variants of concern (VOCs) by the WHO, given their impact on global public health. Based on the epidemiological update by the WHO, five SARS-CoV-2 VOCs have been identified since the beginning of the pandemic:
Alpha (B.1.1.7): first variant of concern described in the United Kingdom (UK) in late December 2020
Beta (B.1.351): first reported in South Africa in December 2020
Gamma(P.1): first reported in Brazil in early January 2021
Despite the unprecedented tốc độ of vaccine development against the prevention of COVID-19 and robust global mass vaccination efforts including vaccine boosters, the emergence of these new SARS-CoV-2 variants threatens khổng lồ overturn the significant progress made so far in limiting the spread of this viral illness.
This review article aims to lớn comprehensively describe the etiology, epidemiology, pathophysiology, clinical features, diagnostic methods, & the latest novel therapeutics in the management of COVID-19. This reviews also briefly provides an overview of the different variants of SARS-CoV-2 & the efficacy of different available vaccines for prevention against COVID-19 & its variants.
Etiology
Coronaviruses (CoVs) are positive-stranded RNA(+ssRNA) viruses with a crown-like appearance under an electron microscope (coronam is the Latin term for crown) due khổng lồ the presence of spike glycoproteins on the envelope. The subfamily Orthocoronavirinae of the Coronaviridae family (order Nidovirales) classifies into four genera of CoVs:
Alphacoronavirus (alphaCoV)
Betacoronavirus (betaCoV)
Deltacoronavirus (deltaCoV)
BetaCoV genus is further divided into five sub-genera or lineages.<1> Genomic characterization has shown that bats and rodents are the probable gene sources of alphaCoVs and betaCoVs. On the contrary, avian species seem khổng lồ represent the gen sources of deltaCoVs & gammaCoVs. CoVs have become the major pathogens of emerging respiratory disease outbreaks. Members of this large family of viruses can cause respiratory, enteric, hepatic, & neurological diseases in different animal species, including camels, cattle, cats, và bats. For reasons yet lớn be explained, these viruses can cross species barriers & can cause, in humans, illness ranging from the common cold lớn more severe diseases such as MERS & SARS. Lớn date, seven human CoVs (HCoVs) capable of infecting humans have been identified. Some of the HCoVs were identified in the mid-1960s, while others were only detected in the new millennium. In general, estimates suggest that 2% of the population are healthy carriers of a CoVs and that these viruses are responsible for about 5% to 10% of acute respiratory infections.<2>
Common human CoVs: HCoV-OC43, và HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, & HCoV-NL63 (alphaCoVs). These viruses can cause common colds và self-limiting upper respiratory tract infections in immunocompetent individuals. However, in immunocompromised subjects and the elderly, lower respiratory tract infections can occur due to lớn these viruses.
Other human CoVs: SARS-CoV và MERS-CoV (betaCoVs of the B & C lineage, respectively). These viruses are considered khổng lồ be more virulent và capable of causing epidemics manifesting with respiratory & extra-respiratory manifestations of variable clinical severity.
SARS-CoV-2 is a novel betaCoV belonging lớn the same subgenus as the severe acute respiratory syndrome coronavirus (SARS-CoV) và the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which have been previously implicated in SARS-CoV và MERS-CoV epidemics with mortality rates up to 10% và 35%, respectively.<3> It has a round or elliptic và often pleomorphic form và a diameter of approximately 60–140 nm. Like other CoVs, it is sensitive khổng lồ ultraviolet rays and heat. In this regard, although high temperature decreases the replication of any species of virus. Currently, the inactivation temperature of SARS-CoV-2 is being researched. A stainless steel surface held at an air temperature of 54.5°C (130 °F) results in the inactivation of 90% of SARS-CoV-2 in approximately 36 minutes. At 54.5°C, the time for a 90% decrease in infectivity was 35.4 ± 9.0 min & the virus half-life was 10.8 ± 3.0 min.<4> Conversely, it may resist lower temperatures even below 0°C. Also, these viruses can be effectively inactivated by lipid solvents, including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid, & chloroform except for chlorhexidine.
Genomic characterization of the new HCoV, isolated from a cluster-patient with atypical pneumonia after visiting Wuhan, had 89% nucleotide identity with bat SARS-like-CoVZXC21 và 82% with that of human SARS-CoV. Hence, it was termed SARS-CoV-2 by experts of the International Committee on Taxonomy of Viruses. The single-stranded RNA genome of SARS-CoV-2 contains 29891 nucleotides, encoding for 9860 amino acids.
Although the origin of SARS-CoV-2 is currently unknown, it is widely postulated to have originated from an animal implicating zoonotic transmission. Genomic analyses suggest that SARS-CoV-2 probably evolved from a strain found in bats. The genomic comparison between the human SARS-CoV-2 sequence & known animal coronaviruses indeed revealed high homology (96%) between the SARS-CoV-2 & the betaCoV RaTG13 of bats (Rhinolophus affinis)<5>Similar khổng lồ SARS and MERS, it has been hypothesized that SARS-CoV-2 advanced from bats lớn intermediate hosts such as pangolins and minks, and then to lớn humans.<6><7> A recently released report by the WHO describing the possible origins of SARS-CoV-2 was inconclusive as it did not clearly specify the origin of the virus; however, it did report that the circulation of SARS-CoV-2 occurred as early as December 2019. This report explored several possible hypotheses of the origin of the vi khuẩn that included the origin of the virus in an animal, the transmission of the virus to lớn an intermediate host, and subsequent passage into humans.
SARS-CoV-2 Variants
As mentioned earlier, SARS-CoV-2 is prone lớn genetic evolution resulting in multiple variants that may have different characteristics compared to its ancestral strains. Periodic genomic sequencing of viral samples is of fundamental importance, especially in a global pandemic setting, as it helps detect any new genetic variants of SARS-CoV-2. Notably, the genetic evolution was minimal initially with the emergence of the globally dominant D614G variant, which was associated with increased transmissibility but without the ability lớn cause severe illness.<8> Another variant was identified in humans, attributed lớn transmission from infected farmed mink in Denmark, which was not associated with increased transmissibility<7>. Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs) due lớn their potential lớn cause enhanced transmissibility or virulence, reduction in neutralization by antibodies obtained through natural infection or vaccination, the ability to lớn evade detection, or a decrease in therapeutics or vaccination effectiveness. With the continued emergence of multiple variants, the CDC and the WHO have independently established a classification system for distinguishing the emerging variants of SARS-CoV-2 into variants of concern(VOCs) and variants of interest(VOIs).
SARS-CoV-2 Variants of Concern (VOCs)
The B.1.1.7 variant emerged as one of the most dominant SARS-CoV-2 strains circulating in the US during the early stage of the pandemic.
SARS-CoV-2 Variants of Interest (VOIs)
VOIs are defined as variants with specific genetic markers that have been associated with changes that may cause enhanced transmissibility or virulence, reduction in neutralization by antibodies obtained through natural infection or vaccination, the ability lớn evade detection, or a decrease in the effectiveness of therapeutics or vaccination. Since the beginning of the pandemic, WHO has described eight variants of interest (VOIs), namely Epsilon (B.1.427 và B.1.429); Zeta (P.2); Eta ( B.1.525); Theta (P.3); Iota (B.1.526); Kappa(B.1.617.1); Lambda(C.37) and Mu (B.1.621); và the CDC has designated the Epsilon (B.1.427 và B.1.429),Eta(B.1.525); Iota (B.1.526); Kappa(B.1.617.1); Zeta (P.2); Mu(B.1.621, B.1.621.1) and B.1.617.3 as VOIs.
In comparison to lớn the current circulating SARS-CoV-2 variants ,previously designated VOCs & VOIs which that are circulating in at negligible levels or are undetectable and do not pose a significant risk lớn global public health are designated as previously circulating VOCs or VOIs by the WHO & Variants Being Monitored (VBM) by the CDC.
Transmission of SARS-CoV-2
The primary mode of transmission of SARS-CoV-2 is via exposure lớn respiratory droplets carrying the infectious virut from close liên hệ or droplet transmission from presymptomatic, asymptomatic, or symptomatic individuals harboring the virus.
Airborne transmission with aerosol-generating procedures has also been implicated in the spread of COVID-19. However, data implicating airborne transmission of SARS-CoV-2 in the absence of aerosol-generating procedures are emerging & being evaluated. However, this mode of transmission has not been universally acknowledged.
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Fomite transmission from contamination of inanimate surfaces with SARS-CoV-2 has been well characterized based on many studies reporting the viability of SARS-CoV-2 on various porous and nonporous surfaces.
The Centers for Disease Control & Prevention(CDC) recently released an update stating that individuals can be infected with SARS-CoV-2 via liên hệ with surfaces contaminated by the virus, but the risk is low và is not the main route of transmission of this virus.
Epidemiology
According to lớn the World Health Organization (WHO), the emergence of viral diseases represents a serious public health risk. In the past two decades, several epidemics caused by viruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) from 2002 khổng lồ 2003, và H1N1 influenza in 2009, và the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 have been described which have had a significant impact on global health. Since being declared a global pandemic by the WHO, SARS-CoV-2, the virut responsible for COVID-19 has spread to lớn 223 countries with more than 593 million cases, and more than 6 million deaths reported globally. A recent epidemiological update by WHO reported that more than 200 countries around the world have reported SARS-Co-V-2 variants of concern of which the Omicron VOC has been reported as the most dominant current circulating VOC since first being reported in November 2021. The U.S. Has experienced the highest number of SARS-CoV-2 infections & COVID-19 related deaths followed by India & Brazil. In fact, COVID-19 was the third leading cause of death in the U.S. In 2020 after heart disease và cancer, with approximately 375,000 death reported.<32> The WHO’s current estimate of the global case fatality rate for COVID-19 is 2.2%. However, the case fatality rate is affected by factors that include age, underlying preexisting conditions, và severity of illness and significantly varies between countries.
Age, Gender-based Differences and The Impact Of Medical Comorbidities in COVID-19
Individuals of all ages are at risk of contracting this infection và severe disease. However, patients aged ≥60 years and patients with underlying medical comorbidities (obesity, cardiovascular disease, chronic kidney disease, diabetes, chronic lung disease, smoking, cancer, solid organ or hematopoietic stem cell transplant patients) have an increased risk of developing severe COVID-19 infection. The percentage of COVID-19 patients requiring hospitalization was six times higher in those with preexisting medical conditions than those without medical conditions (45.4% vs. 7.6%) based on an analysis by Stokes et al. Of confirmed cases reported lớn the CDC during January 22 lớn May 30, 2020. Notably, the study also reported that the percentage of patients who succumbed to this illness was 12 times higher in those with preexisting medical conditions than those without medical conditions (19.5% vs. 1.6%).<33> Data regarding the gender-based differences in COVID-19 suggests that male patients are at risk of developing severe illness and increased mortality due to lớn COVID-19 compared khổng lồ female patients.<34><35> Results from a retrospective cohort study from March 1 khổng lồ November 21, 2020, evaluating the mortality rate in 209 US acute care hospitals that included 42 604 patients with confirmed SARS-CoV-2 infection, reported a higher mortality rate in male patients (12.5%) compared to lớn female patients (9.6%).<36>
Racial and Ethnic Disparities in COVID-19
The severity of infection & mortality related to COVID-19 also varies between different ethnic groups.<30> Racial & ethnic minority groups were reported to lớn have a higher percentage of COVID-19 related hospitalizations than trắng patients based on a recent CDC analysis of hospitalizations from a large administrative database that included approximately 300,000 COVID-19 patients hospitalized from March 2020 lớn December 2020. This high percentage of COVID-19 related hospitalizations among racial and ethnic groups was driven by a higher risk for exposure to lớn SARS-CoV-2 và an increased risk for developing severe COVID-19 disease.<37> The results of a meta-analysis of 50 studies from the US và UK researchers noted that people of Black, Hispanic, & Asian ethnic minority groups are at increased risk of contracting and dying from COVID-19 infection.<38> COVID-19 related death rates were the highest among Hispanic persons.<32> Another analysis by the CDC evaluating the risk of COVID-19 among sexual minority adults reported that underlying medical comorbidities which increase the risk of developing severe COVID-19 were more prevalent in sexual minority individuals than heterosexual individuals both within the general population và within specific racial/ethnic groups.<39>
Pathophysiology
The general description of viral structure and its genome of CoVs is essential for addressing the pathogenesis of SARS-CoV-2. As described earlier, CoVs are enveloped, positive-stranded RNA viruses with a nucleocapsid, & the genomic structure is organized in a +ssRNA of approximately 30 kb in length và with a 5′-cap structure and 3′-poly-A tail making it the largest among RNA viruses. Upon entry into the host, replication of the viral RNA is initiated with the synthesis of polyprotein 1a/1ab (pp1a/pp1ab). The transcription occurs through the replication-transcription complex (RCT) organized in double-membrane vesicles and via the synthesis of subgenomic RNAs (sgRNAs) sequences. Conversely, transcription termination occurs at transcription regulatory sequences, located between the so-called open reading frames (ORFs) that work as templates for the production of subgenomic mRNAs. In an atypical CoV genome, at least six ORFs can be present. Among these, a frameshift between ORF1a and ORF1b guides the production of both pp1a và pp1ab polypeptides that are processed by virally encoded chymotrypsin-like protease (3CLpro) or main protease (Mpro), as well as one or two papain-like proteases for producing 16 with known or predicted RNA synthesis & modification functions non-structural proteins (NSPs 1-16). Besides ORF1a & ORF1b, other ORFs encode structural proteins, including spike, membrane, envelope, & nucleocapsid proteins và accessory proteic chains.<3>. Different CoVs possess unique structural và accessory proteins translated by dedicated sgRNAs.The pathogenesis of CoVs and SARS-CoV-2 is related khổng lồ the function of the NSPs & structural proteins. For example, researchers have outlined the role of NSPs in blocking the host"s innate immune response.<2> Among functions of structural proteins, the envelope has a crucial role in virut pathogenicity as it promotes viral assembly và release. Among the structural elements of CoVs, there are the spike glycoproteins composed of two subunits (S1 and S2). Homotrimers of S proteins compose the spikes on the viral surface, guiding the links to host receptors.<40>
Pathogenesis of SARS-CoV-2
Structurally & phylogenetically, SARS-CoV-2 is similar to SARS-CoV and MERS-CoV & is composed of four main structural proteins: spike (S), envelope (E) glycoprotein, nucleocapsid (N), membrane (M) protein, along with 16 nonstructural proteins, và 5-8 accessory proteins.<41> The surface spike (S) glycoprotein, which resembles a crown, is located on the outer surface of the virion và undergoes cleavage into an amino (N)-terminal S1 subunit, which facilitates the incorporation of the vi khuẩn into the host cell and a carboxyl (C)-terminal S2 subunit containing a fusion peptide, a transmembrane domain, & cytoplasmic domain is responsible for virus-cell membrane fusion.<42><43> The S1 subunit is further divided into a receptor-binding tên miền (RBD) và N-terminal domain (NTD), which facilitates viral entry into the host cell & serves as a potential target for neutralization in response lớn antisera or vaccines.<40> The RBD is a fundamental peptide domain name in the pathogenesis of infection as it represents a binding site for the human angiotensin-converting enzyme 2 (ACE2) receptors. Inhibition of the renin-angiotensin-aldosterone system(RAAS), as previously hypothesized, does not increase the risk of hospitalization for COVID-19 and severe disease.<44>
SARS-CoV-2 gains entry into the hosts" cells by binding the SARS-CoV-2 spike or S protein (S1) khổng lồ the ACE2 receptors abundantly on respiratory epithelium such as type II alveolar epithelial cells. Besides the respiratory epithelium, ACE2 receptors are also expressed by other organs such as the upper esophagus, enterocytes from the ileum, myocardial cells, proximal tubular cells of the kidney, và urothelial cells of the bladder.<45> The viral attachment process is followed by priming the spike protein S2 subunit by the host transmembrane serine protease 2 (TMPRSS2) that facilitates cell entry và subsequent viral replication endocytosis with the assembly of virions.<46>
In summary, the spike RBD allows the binding khổng lồ the ACE2 receptor in the lungs and other tissues. The spike protein of an amino acid site (polybasic site) allows the functional processing of the same by the human enzyme furin (protease). This process enables the exposure of the fusion sequences and, therefore, the fusion of the viral & cell membranes, a necessary passage for the virus khổng lồ enter the cell.
Effect of SARS-CoV-2 on the Respiratory System/Pathogenesis of SARS-CoV-2-induced Pneumonia
COVID-19 is primarily considered a viral respiratory and vascular illness as its causative agent, SARS-CoV-2, predominantly targets the respiratory và vascular systems.
The pathogenesis of SARS-CoV-2 induced pneumonia is best explained by two stages, an early và a late phase. The early phase is characterized by viral replication resulting in direct virus-mediated tissue damage, which is followed by a late phase when the infected host cells trigger an immune response with the recruitment of T lymphocytes, monocytes, và neutrophil recruitment which releases cytokines such as tumor necrosis factor-α (TNF α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), ), IL-1β, IL-8, IL-12 và interferon (IFN)-γ. In severe COVID-19, the immune system"s overactivation results in a "cytokine storm" characterized by the release of high levels of cytokines, especially IL-6 & TNF-α, into the circulation, causing a local & systemic inflammatory response.<47><48> The increased vascular permeability và subsequent development of pulmonary edema in patients with severe COVID-19 are explained by multiple mechanisms, which includes a) endotheliitis as a result of direct viral injury và perivascular inflammation leading khổng lồ microvascular và microthrombi deposition b) dysregulation of the RAAS due khổng lồ increased binding of the virus to the ACE2 receptors & c)activation of the kallikrein- bradykinin pathway, the activation of which enhances vascular permeability, d)enhanced epithelial cell contraction causing swelling of cells và disturbance of intercellular junctions.<49><50><51> Besides IL-6 & TNF-α, the binding of SARS-CoV-2 khổng lồ 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, until fibrosis.<52>
Effect of SARS-CoV-2 on Extrapulmonary Organ Systems
Although the respiratory system is the principal target for SARS-CoV-2 as described above, it can affect other major organ systems such as the gastrointestinal tract (GI), hepatobiliary, cardiovascular, renal, & central nervous system. SARS-CoV-2–induced organ dysfunction, in general, is possibly explained by either one or a combination of the proposed mechanisms such as direct viral toxicity, ischemic injury caused by vasculitis, thrombosis, or thrombo-inflammation, immune dysregulation, và renin-angiotensin-aldosterone system (RAAS) dysregulation.<53>
