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Tuesday, March 14, 2023

Histrionic personality disorder

From Wikipedia, the free encyclopedia
 
Histrionic personality disorder
Two masks, one is white and smiling, the other is black and depressed
Dramatic behavior is a key marker of histrionic personality disorder

SpecialtyClinical Psychology, Psychiatry
SymptomsPersistent attention seeking, dramatic behavior, rapidly shifting and shallow emotions, sexually provocative behavior, undetailed style of speech, and a tendency to consider relationships more intimate than they actually are.
Usual onsetSymptoms typically do not fully develop until the age of 15
DurationLifelong
CausesHighly responsive noradrenergic systems, genetics, authoritarian parenting
Diagnostic methodBased on symptoms
Differential diagnosisOther personality disorders, Substance abuse disorders, and personality change due to another medical condition
TreatmentFunctional analytic psychotherapy, functional ideographic assessment template, and coding client and therapist behaviors

Histrionic personality disorder (HPD) is defined by the American Psychiatric Association as a personality disorder characterized by a pattern of excessive attention-seeking behaviors, usually beginning in early childhood, including inappropriate seduction and an excessive desire for approval. People diagnosed with the disorder are said to be lively, dramatic, vivacious, enthusiastic, extroverted and flirtatious.

HPD lies in the dramatic cluster of personality disorders. People with HPD have a high desire for attention, make loud and inappropriate appearances, exaggerate their behaviors and emotions, and crave stimulation. They may exhibit sexually provocative behavior, express strong emotions with an impressionistic style, and can be easily influenced by others. Associated features include egocentrism, self-indulgence, continuous longing for appreciation, and persistent manipulative behavior to achieve their own wants.

Signs and symptoms

People diagnosed with HPD may be dramatic. They often fail to see their own personal situation realistically, instead dramatizing and exaggerating their difficulties. Patients with this disorder can have rapidly shifting emotions and a decreased ability to recognize other's emotions. Their emotions may appear superficial or exaggerated to others. This disorder is associated with extraversion, a lower tolerance for frustration or delayed gratification, and openness to new experiences. People with HPD may have little self-doubt and often appear egocentric.

Research has also shown those with histrionic personality have a greater desire for social approval and reassurance and will constantly seek it out, making those with HPD more vulnerable to social media addiction. People with this disorder often display excessive sensitivity to criticism or disapproval. They will work hard to get others to pay attention to them, possibly as a method of testing the stability of relationships. They may enjoy situations in which they can be the center of attention, and may feel uncomfortable when people are not paying attention to them. It is common for people with this disorder to wear flamboyant clothing, try body modifications, and fake medical conditions in an attempt to draw other's attention. They may display inappropriately sexually provocative, flirtatious, or exploitative behavior. Sexting and exhibitionist behavior are also behaviors people with this condition sometimes exhibit. Some people with histrionic traits or personality disorder change their seduction technique into a more maternal or paternal style as they age. When their desire for attention is not met, it can heighten the severity of their symptoms. They tend to be impressionable and easily manipulatable, especially by those they respect.

Patients with HPD are usually high-functioning, both socially and professionally. They usually have good social skills, despite tending to use them to make themselves the center of attention. HPD may also affect a person's social and romantic relationships, as well as their ability to cope with losses or failures. People with HPD tend to consider relationships closer than they usually are. They may seek treatment for clinical depression when romantic (or other close personal) relationships end. Substance disorders, such as alcohol use disorder or opioid use disorder, are all common in patients with histrionic personality disorder. They are also at higher risks of suicide, body dysmorphia, and divorce. They may go through frequent job changes, as they become easily bored and may prefer withdrawing from frustration (instead of facing it). Because they tend to crave novelty and excitement, they may place themselves in risky situations. All of these factors may lead to greater risk of developing clinical depression. People with this condition can have an impressionistic and undetailed style of speech.

Despite these traits, they can be prideful of their own personality, and may be unwilling to change, viewing any change as a threat. They may even blame their personal failures or disappointments on others.

Causes

Little research has been done to find evidence of what causes histrionic personality disorder. Although direct causes are inconclusive, various theories and studies suggest multiple possible causes, of a neurochemical, genetic, psychoanalytic, or environmental nature. Traits such as extravagance, vanity, and seductiveness of hysteria have similar qualities to women diagnosed with HPD. HPD symptoms typically do not fully develop until the age of 15, while the onset of treatment only occurs, on average, at approximately 40 years of age.

Neurochemical/physiological

Studies have shown that there is a strong correlation between the function of neurotransmitters and the Cluster B personality disorders such as HPD. Individuals diagnosed with HPD have a highly responsive noradrenergic system, which is responsible for the synthesis, storage, and release of the neurotransmitter norepinephrine. High levels of norepinephrine lead to anxiety-proneness, dependency, and high sociability.

Genetic

Twin studies have aided in breaking down the genetic vs. environment debate. A twin study conducted by the Department of Psychology at Oslo University attempted to establish a correlation between genetics and Cluster B personality disorders. With a test sample of 221 twins, 92 monozygotic and 129 dizygotic, researchers interviewed the subjects using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and concluded that there was a correlation of 0.67 that histrionic personality disorder is hereditary.

Psychoanalytic theory

Though criticised as being unsupported by scientific evidence, psychoanalytic theories incriminate authoritarian or distant attitudes by one (mainly the mother) or both parents, along with conditional love based on expectations the child can never fully meet. Using psychoanalysis, Freud believed that lustfulness was a projection of the patient's lack of ability to love unconditionally and develop cognitively to maturity, and that such patients were overall emotionally shallow. He believed the reason for being unable to love could have resulted from a traumatic experience, such as the death of a close relative during childhood or divorce of one's parents, which gave the wrong impression of committed relationships. Exposure to one or multiple traumatic occurrences of a close friend or family member's leaving (via abandonment or mortality) would make the person unable to form true and affectionate attachments towards other people.

HPD and antisocial personality disorder

Another theory suggests a possible relationship between histrionic personality disorder and antisocial personality disorder. Research has found 2/3 of patients diagnosed with histrionic personality disorder also meet criteria similar to those of the antisocial personality disorder, which suggests both disorders based towards sex-type expressions may have the same underlying cause.

Some family history studies have found that histrionic personality disorder, as well as borderline and antisocial personality disorders, tend to run in families, but it is unclear how much is due to genetic versus environmental factors. Both examples suggest that predisposition could be a factor as to why certain people are diagnosed with histrionic personality disorder, however little is known about whether or not the disorder is influenced by any biological compound or is genetically inheritable. Little research has been conducted to determine the biological sources, if any, of this disorder.

Diagnosis

The person's appearance, behavior and history, along with a psychological evaluation, are usually sufficient to establish a diagnosis. There is no test to confirm this diagnosis. Because the criteria are subjective, some people may be wrongly diagnosed.

DSM 5

The current edition of the Diagnostic and Statistical Manual of Mental Disorders, DSM 5, defines histrionic personality disorder (in Cluster B) as:

A pervasive pattern of excessive emotionality and attention-seeking, beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:

  • is uncomfortable in situations in which he or she is not the center of attention
  • interaction with others is often characterized by inappropriate sexually seductive or provocative behavior
  • displays rapidly shifting and shallow expression of emotions
  • consistently uses physical appearance to draw attention to self
  • has a style of speech that is excessively impressionistic and lacking in detail
  • shows self-dramatization, theatricality, and exaggerated expression of emotion
  • is suggestible, i.e., easily influenced by others or circumstances
  • considers relationships to be more intimate than they actually are

The DSM 5 requires that a diagnosis for any specific personality disorder also satisfies a set of general personality disorder criteria.

ICD-10

The World Health Organization's ICD-10 lists histrionic personality disorder (F60.4) as:

A personality disorder characterized by:

  • shallow and labile affectivity,
  • self-dramatization,
  • theatricality,
  • exaggerated expression of emotions,
  • suggestibility,
  • egocentricity,
  • self-indulgence,
  • lack of consideration for others,
  • easily hurt feelings, and
  • continuous seeking for appreciation, excitement and attention.

It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.

Comorbidity

Most histrionics also have other mental disorders. Comorbid conditions include: antisocial, dependent, borderline, and narcissistic personality disorders, as well as depression, anxiety disorders, panic disorder, somatoform disorders, anorexia nervosa, substance use disorder and attachment disorders, including reactive attachment disorder.

Millon's subtypes

In 2000, Theodore Millon suggested six subtypes of histrionic personality disorder. Any individual histrionic may exhibit one or more of the following:

Subtype Personality Traits
Appeasing histrionic (Including dependent and compulsive features) Seeks to placate, mend, patch up, smooth over troubles; knack for settling differences, moderating tempers by yielding, compromising, conceding; sacrifices self for commendation; fruitlessly placates the unplacatable.
Vivacious histrionic (including hypomanic features, and possibly

narcissistic features)

Vigorous, charming, bubbly, brisk, spirited, flippant, impulsive; seeks momentary cheerfulness and playful adventures; animated, energetic, ebullient.
Tempestuous histrionic (Including negativistic features) Impulsive, out of control; moody complaints, sulking; precipitous emotion, stormy, impassioned, easily wrought-up, periodically inflamed, turbulent.
Disingenuous histrionic (Including antisocial features) Underhanded, double-dealing, scheming, contriving, plotting, crafty, false-hearted; egocentric, insincere, deceitful, calculating, guileful.
Theatrical histrionic (Variant of “pure” pattern) Affected, mannered, put-on; postures are striking, eyecatching, graphic; markets self-appearance; is synthesized, stagy; simulates desirable/dramatic poses.
Infantile histrionic (Including borderline features) Labile, high-strung, volatile emotions; childlike hysteria and nascent pouting; demanding, overwrought; fastens and clutches to another; is excessively attached, hangs on, stays fused to and clinging.

Treatment

Treatment is often prompted by depression associated with dissolved romantic relationships. Medication does little to affect the personality disorder, but may be helpful with symptoms such as depression. Treatment for HPD itself involves psychotherapy, including cognitive therapy.

Interviews and self-report methods

In general clinical practice with assessment of personality disorders, one form of interview is the most popular: an unstructured interview. The actual preferred method is a semi-structured interview but there is reluctance to use this type of interview because they can seem impractical or superficial. The reason that a semi-structured interview is preferred over an unstructured interview is that semi-structured interviews tend to be more objective, systematic, replicable, and comprehensive. Unstructured interviews, despite their popularity, tend to have problems with unreliability and are susceptible to errors leading to false assumptions of the patient.

One of the single most successful methods for assessing personality disorders by researchers of normal personality functioning is the self-report inventory following up with a semi-structured interview. There are some disadvantages with the self-report inventory method that with histrionic personality disorder there is a distortion in character, self-presentation, and self-image. This cannot be assessed simply by asking most clients if they match the criteria for the disorder. Most projective testing depend less on the ability or willingness of the person to provide an accurate description of the self, but there is currently limited empirical evidence on projective testing to assess histrionic personality disorder.

Functional analytic psychotherapy

Another way to treat histrionic personality disorder after identification is through functional analytic psychotherapy. The job of a Functional Analytic Psychotherapist is to identify the interpersonal problems with the patient as they happen in session or out of session. Initial goals of functional analytic psychotherapy are set by the therapist and include behaviors that fit the client's needs for improvement. Functional analytic psychotherapy differs from the traditional psychotherapy due to the fact that the therapist directly addresses the patterns of behavior as they occur in-session.

The in-session behaviors of the patient or client are considered to be examples of their patterns of poor interpersonal communication and to adjust their neurotic defenses. To do this, the therapist must act on the client's behavior as it happens in real time and give feedback on how the client's behavior is affecting their relationship during therapy. The therapist also helps the client with histrionic personality disorder by denoting behaviors that happen outside of treatment; these behaviors are termed "Outside Problems" and "Outside Improvements". This allows the therapist to assist in problems and improvements outside of session and to verbally support the client and condition optimal patterns of behavior". This then can reflect on how they are advancing in-session and outside of session by generalizing their behaviors over time for changes or improvement".

Coding client and therapist behaviors

In these sessions there is a certain set of dialogue or script that can be forced by the therapist for the client to give insight on their behaviors and reasoning". Here is an example from" the conversation is hypothetical. T = therapist C = Client This coded dialogue can be transcribed as:

  • ECRB – Evoking clinically relevant behavior
    • T: Tell me how you feel coming in here today (CRB2) C: Well, to be honest, I was nervous. Sometimes I feel worried about how things will go, but I am really glad I am here.
  • CRB1 – In-session problems
    • C: Whatever, you always say that. (becomes quiet). I don't know what I am doing talking so much.
  • CRB2 – In-session improvements
  • TCRB1 – Clinically relevant response to client problems
    • T: Now you seem to be withdrawing from me. That makes it hard for me to give you what you might need from me right now. What do you think you want from me as we are talking right now?".
  • TCRB2 – Responses to client improvement
    • T: That's great. I am glad you're here, too. I look forward to talking to you.

Functional ideographic assessment template

Another example of treatment besides coding is functional ideographic assessment template. The functional ideographic assessment template, also known as FIAT, was used as a way to generalize the clinical processes of functional analytic psychotherapy. The template was made by a combined effort of therapists and can be used to represent the behaviors that are a focus for this treatment. Using the FIAT therapists can create a common language to get stable and accurate communication results through functional analytic psychotherapy at the ease of the client; as well as the therapist.

Epidemiology

The survey data from the National epidemiological survey from 2001 to 2002 suggests a prevalence of HPD of 1.84 percent. Major character traits may be inherited, while other traits may be due to a combination of genetics and environment, including childhood experiences. This personality is seen more often in women than in men. Approximately 65% of HPD diagnoses are women while 35% are men. In Marcie Kaplan's A Women's View of DSM-III, she argues that women are overdiagnosed due to potential biases and expresses that even healthy women are often automatically diagnosed with HPD. It has also been argued due to diagnostic bias that prevalence rates are equal among women and men.

Many symptoms representing HPD in the DSM are exaggerations of traditional feminine behaviors. In a peer and self-review study, it showed that femininity was correlated with histrionic, dependent and narcissistic personality disorders. Although two thirds of HPD diagnoses are female, there have been a few exceptions. Whether or not the rate will be significantly higher than the rate of women within a particular clinical setting depends upon many factors that are mostly independent of the differential sex prevalence for HPD. Those with HPD are more likely to look for multiple people for attention, which leads to marital problems due to jealousy and lack of trust from the other party. This makes them more likely to become divorced or separated once married. With few studies done to find direct causations between HPD and culture, cultural and social aspects play a role in inhibiting and exhibiting HPD behaviors.

SARS-CoV-2

From Wikipedia, the free encyclopedia
Severe acute respiratory syndrome coronavirus 2
Electron micrograph of SARS-CoV-2 virions with visible coronae
Colourised transmission electron micrograph of SARS-CoV-2 virions with visible coronae

Illustration of a SARS-CoV-2 virion
Model of the external structure of the SARS-CoV-2 virion
Blue:envelope
Turquoise:spike glycoprotein (S)
Red:envelope proteins (E)
Green:membrane proteins (M)
Orange:glycan
Virus classification e
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Species:
Virus:
Severe acute respiratory syndrome coronavirus 2
Notable variants
Synonyms
  • 2019-nCoV

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a provisional name, 2019 novel coronavirus (2019-nCoV), and has also been called the human coronavirus 2019 (HCoV-19 or hCoV-19). First identified in the city of Wuhan, Hubei, China, the World Health Organization declared the outbreak a public health emergency of international concern on January 30, 2020, and a pandemic on March 11, 2020. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans.

SARS‑CoV‑2 is a virus of the species severe acute respiratory syndrome–related coronavirus (SARSr-CoV), related to the SARS-CoV-1 virus that caused the 2002–2004 SARS outbreak. Despite its close relation to SARS-CoV-1, its closest known relatives, with which it forms a sister group, are the derived SARS viruses BANAL-52 and RaTG13. Available evidence indicates that it is most likely of zoonotic origin and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus. Research is ongoing as to whether SARS‑CoV‑2 came directly from bats or indirectly through any intermediate hosts. The virus shows little genetic diversity, indicating that the spillover event introducing SARS‑CoV‑2 to humans is likely to have occurred in late 2019.

Epidemiological studies estimate that, in the December 2019–September 2020 period, each infection resulted in an average of 2.4–3.4 new infections when no members of the community are immune and no preventive measures are taken. However, some subsequent variants have become more infectious. The virus is airborne and primarily spreads between people through close contact and via aerosols and respiratory droplets that are exhaled when talking, breathing, or otherwise exhaling, as well as those produced from coughs and sneezes. It enters human cells by binding to angiotensin-converting enzyme 2 (ACE2), a membrane protein that regulates the renin–angiotensin system.

Terminology

Sign with provisional name "2019-nCoV"

During the initial outbreak in Wuhan, China, various names were used for the virus; some names used by different sources included "the coronavirus" or "Wuhan coronavirus". In January 2020, the World Health Organization (WHO) recommended "2019 novel coronavirus" (2019-nCoV) as the provisional name for the virus. This was in accordance with WHO's 2015 guidance against using geographical locations, animal species, or groups of people in disease and virus names.

On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS‑CoV‑2). To avoid confusion with the disease SARS, the WHO sometimes refers to SARS‑CoV‑2 as "the COVID-19 virus" in public health communications and the name HCoV-19 was included in some research articles. Referring to COVID-19 as the "Wuhan virus" has been described as dangerous by WHO officials, and as xenophobic by University of California at Berkeley Asian American studies lecturer Harvey Dong.

Infection and transmission

Human-to-human transmission of SARS‑CoV‑2 was confirmed on 20 January 2020 during the COVID-19 pandemic. Transmission was initially assumed to occur primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft). Laser light scattering experiments suggest that speaking is an additional mode of transmission and a far-reaching one, indoors, with little air flow. Other studies have suggested that the virus may be airborne as well, with aerosols potentially being able to transmit the virus. During human-to-human transmission, between 200 and 800 infectious SARS‑CoV‑2 virions are thought to initiate a new infection. If confirmed, aerosol transmission has biosafety implications because a major concern associated with the risk of working with emerging viruses in the laboratory is the generation of aerosols from various laboratory activities which are not immediately recognizable and may affect other scientific personnel. Indirect contact via contaminated surfaces is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic (polypropylene) and stainless steel (AISI 304) for up to three days, but it does not survive on cardboard for more than one day or on copper for more than four hours. The virus is inactivated by soap, which destabilizes its lipid bilayer. Viral RNA has also been found in stool samples and semen from infected individuals.

The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection or in the first week of symptoms and declines thereafter. The duration of SARS-CoV-2 RNA shedding is generally between 3 and 46 days after symptom onset.

A study by a team of researchers from the University of North Carolina found that the nasal cavity is seemingly the dominant initial site of infection, with subsequent aspiration-mediated virus-seeding into the lungs in SARS‑CoV‑2 pathogenesis. They found that there was an infection gradient from high in proximal towards low in distal pulmonary epithelial cultures, with a focal infection in ciliated cells and type 2 pneumocytes in the airway and alveolar regions respectively.

Studies have identified a range of animals—such as cats, ferrets, hamsters, non-human primates, minks, tree shrews, raccoon dogs, fruit bats, and rabbits—that are susceptible and permissive to SARS-CoV-2 infection. Some institutions have advised that those infected with SARS‑CoV‑2 restrict their contact with animals.

Asymptomatic and presymptomatic transmission

On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". One meta-analysis found that 17% of infections are asymptomatic, and asymptomatic individuals were 42% less likely to transmit the virus.

However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections. That may explain how out of 217 on board a cruise liner that docked at Montevideo, only 24 of 128 who tested positive for viral RNA showed symptoms. Similarly, a study of ninety-four patients hospitalized in January and February 2020 estimated patients began shedding virus two to three days before symptoms appear and that "a substantial proportion of transmission probably occurred before first symptoms in the index case". The authors later published a correction that showed that shedding began earlier than first estimated, four to five days before symptoms appear.

Reinfection

There is uncertainty about reinfection and long-term immunity. It is not known how common reinfection is, but reports have indicated that it is occurring with variable severity.

The first reported case of reinfection was a 33-year-old man from Hong Kong who first tested positive on 26 March 2020, was discharged on 15 April 2020 after two negative tests, and tested positive again on 15 August 2020 (142 days later), which was confirmed by whole-genome sequencing showing that the viral genomes between the episodes belong to different clades. The findings had the implications that herd immunity may not eliminate the virus if reinfection is not an uncommon occurrence and that vaccines may not be able to provide lifelong protection against the virus.

Another case study described a 25-year-old man from Nevada who tested positive for SARS‑CoV‑2 on 18 April 2020 and on 5 June 2020 (separated by two negative tests). Since genomic analyses showed significant genetic differences between the SARS‑CoV‑2 variant sampled on those two dates, the case study authors determined this was a reinfection. The man's second infection was symptomatically more severe than the first infection, but the mechanisms that could account for this are not known.

Reservoir and origin

Transmission of SARS-CoV-1 and SARS‑CoV‑2 from mammals as biological carriers to humans

No natural reservoir for SARS-CoV-2 has been identified. Prior to the emergence of SARS-CoV-2 as a pathogen infecting humans, there had been two previous zoonosis-based coronavirus epidemics, those caused by SARS-CoV-1 and MERS-CoV.

The first known infections from SARS‑CoV‑2 were discovered in Wuhan, China. The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event. Because many of the early infectees were workers at the Huanan Seafood Market, it has been suggested that the virus might have originated from the market. However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections. A March 2021 WHO-convened report stated that human spillover via an intermediate animal host was the most likely explanation, with direct spillover from bats next most likely. Introduction through the food supply chain and the Huanan Seafood Market was considered another possible, but less likely, explanation. An analysis in November 2021, however, said that the earliest-known case had been misidentified and that the preponderance of early cases linked to the Huanan Market argued for it being the source.

SARS-CoV-2 has been detected in retroactive testing of samples collected before the recognized start of the pandemic. These detections remain controversal due to the possibility of false positive results. The Lombardy region of Italy was a significant epicenter of the outbreak in early 2020. Although the first recognized case in Italy was on February 20, 2020, contact tracing determined the virus was circulating in January. Sewage samples collected in Milan and Turin going back to June 2019 were tested and found to contain viral RNA starting from December 18, 2019. Antibodies to SARS-CoV-2 were found in blood samples dating back to September 2019, and viral DNA was present in a skin sample collected in Milan on September 12, 2019. This evidence does not contradict an origin of the virus in China, but it suggests that SARS-CoV-2 was infectious to humans and circulating outside China earlier than the hypothesized origins in November 2019. Some scientists have dismissed these detections as false positives; however, some results have been confirmed with fluorescence in situ hybridization and RNA sequencing.

For a virus recently acquired through a cross-species transmission, rapid evolution is expected. The mutation rate estimated from early cases of SARS-CoV-2 was of 6.54×10−4 per site per year. Coronaviruses in general have high genetic plasticity, but SARS-CoV-2's viral evolution is slowed by the RNA proofreading capability of its replication machinery. For comparison, the viral mutation rate in vivo of SARS-CoV-2 has been found to be lower than that of influenza.

Research into the natural reservoir of the virus that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses, most originating in horseshoe bats. The closest match by far, published in Nature (journal) in February 2022, were viruses BANAL-52 (96.8% resemblance to SARS‑CoV‑2), BANAL-103 and BANAL-236, collected in three different species of bats in Feuang, Laos. An earlier source published in February 2020 identified the virus RaTG13, collected in bats in Mojiang, Yunnan, China to be the closest to SARS‑CoV‑2, with 96.1% resemblance. None of the above are its direct ancestor.

Samples taken from Rhinolophus sinicus, a species of horseshoe bats, show an 80% resemblance to SARS‑CoV‑2.

Bats are considered the most likely natural reservoir of SARS‑CoV‑2. Differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans may have been infected via an intermediate host; although the source of introduction into humans remains unknown.

Although the role of pangolins as an intermediate host was initially posited (a study published in July 2020 suggested that pangolins are an intermediate host of SARS‑CoV‑2-like coronaviruses), subsequent studies have not substantiated their contribution to the spillover. Evidence against this hypothesis includes the fact that pangolin virus samples are too distant to SARS-CoV-2: isolates obtained from pangolins seized in Guangdong were only 92% identical in sequence to the SARS‑CoV‑2 genome (matches above 90 percent may sound high, but in genomic terms it is a wide evolutionary gap). In addition, despite similarities in a few critical amino acids, pangolin virus samples exhibit poor binding to the human ACE2 receptor.

Phylogenetics and taxonomy

Genomic information
SARS-CoV-2 genome.svg
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
NCBI genome ID86693
Genome size29,903 bases
Year of completion2020
Genome browser (UCSC)

SARS‑CoV‑2 belongs to the broad family of viruses known as coronaviruses. It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment. Coronaviruses infect humans, other mammals, including livestock and companion animals, and avian species. Human coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS, fatality rate ~34%). SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.

Like the SARS-related coronavirus implicated in the 2003 SARS outbreak, SARS‑CoV‑2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B). Coronaviruses undergo frequent recombination. The mechanism of recombination in unsegmented RNA viruses such as SARS-CoV-2 is generally by copy-choice replication, in which gene material switches from one RNA template molecule to another during replication. The SARS-CoV-2 RNA sequence is approximately 30,000 bases in length, relatively long for a coronavirus—which in turn carry the largest genomes among all RNA families. Its genome consists nearly entirely of protein-coding sequences, a trait shared with other coronaviruses.

Micrograph of SARS‑CoV‑2 virus particles isolated from a patient
Transmission electron micrograph of SARS‑CoV‑2 virions (red) isolated from a patient during the COVID-19 pandemic

A distinguishing feature of SARS‑CoV‑2 is its incorporation of a polybasic site cleaved by furin, which appears to be an important element enhancing its virulence. It was suggested that the acquisition of the furin-cleavage site in the SARS-CoV-2 S protein was essential for zoonotic transfer to humans. The furin protease recognizes the canonical peptide sequence RX[R/K] R↓X where the cleavage site is indicated by a down arrow and X is any amino acid. In SARS-CoV-2 the recognition site is formed by the incorporated 12 codon nucleotide sequence CCT CGG CGG GCA which corresponds to the amino acid sequence P RR A. This sequence is upstream of an arginine and serine which forms the S1/S2 cleavage site (P RR A RS) of the spike protein. Although such sites are a common naturally-occurring feature of other viruses within the Subfamily Orthocoronavirinae, it appears in few other viruses from the Beta-CoV genus, and it is unique among members of its subgenus for such a site. The furin cleavage site PRRAR↓ is highly similar to that of the feline coronavirus, an alphacoronavirus 1 strain.

Viral genetic sequence data can provide critical information about whether viruses separated by time and space are likely to be epidemiologically linked. With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS‑CoV‑2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions; the number of genomes increased to 42 by 30 January 2020. A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a common ancestor", implying that the first human infection occurred in November or December 2019. Examination of the topology of the phylogenetic tree at the start of the pandemic also found high similarities between human isolates. As of 21 August 2021, 3,422 SARS‑CoV‑2 genomes, belonging to 19 strains, sampled on all continents except Antarctica were publicly available.

On 11 February 2020, the International Committee on Taxonomy of Viruses announced that according to existing rules that compute hierarchical relationships among coronaviruses based on five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus from the 2003 SARS outbreak were insufficient to make them separate viral species. Therefore, they identified 2019-nCoV as a virus of Severe acute respiratory syndrome–related coronavirus.

In July 2020, scientists reported that a more infectious SARS‑CoV‑2 variant with spike protein variant G614 has replaced D614 as the dominant form in the pandemic.

Coronavirus genomes and subgenomes encode six open reading frames (ORFs). In October 2020, researchers discovered a possible overlapping gene named ORF3d, in the SARS‑CoV‑2 genome. It is unknown if the protein produced by ORF3d has any function, but it provokes a strong immune response. ORF3d has been identified before, in a variant of coronavirus that infects pangolins.

Phylogenetic tree

A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is:

SARS‑CoV‑2 related coronavirus

(Bat) Rc-o319, 81% to SARS-CoV-2, Rhinolophus cornutus, Iwate, Japan





Bat SL-ZXC21, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang



Bat SL-ZC45, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang





Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica, smuggled from Southeast Asia




Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica, smuggled from Southeast Asia





Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia



Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia





(Bat) RacCS203, 91.5% to SARS-CoV-2, Rhinolophus acuminatus, Chachoengsao, Thailand



(Bat) RmYN02, 93.3% to SARS-CoV-2, Rhinolophus malayanus, Mengla, Yunnan




(Bat) RpYN06, 94.4% to SARS-CoV-2, Rhinolophus pusillus, Xishuangbanna, Yunnan




(Bat) RaTG13, 96.1% to SARS-CoV-2, Rhinolophus affinis, Mojiang, Yunnan



(Bat) BANAL-52, 96.8% to SARS-CoV-2, Rhinolophus malayanus, Vientiane, Laos



SARS-CoV-2









Variants

False-colour transmission electron micrograph of a B.1.1.7 variant coronavirus. The variant's increased transmissibility is believed to be due to changes in the structure of the spike proteins, shown here in green.

There are many thousands of variants of SARS-CoV-2, which can be grouped into the much larger clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).

Several notable variants of SARS-CoV-2 emerged in late 2020. The World Health Organization has currently declared five variants of concern, which are as follows:

  • Alpha: Lineage B.1.1.7 emerged in the United Kingdom in September 2020, with evidence of increased transmissibility and virulence. Notable mutations include N501Y and P681H.
  • Beta: Lineage B.1.351 emerged in South Africa in May 2020, with evidence of increased transmissibility and changes to antigenicity, with some public health officials raising alarms about its impact on the efficacy of some vaccines. Notable mutations include K417N, E484K and N501Y.
  • Gamma: Lineage P.1 emerged in Brazil in November 2020, also with evidence of increased transmissibility and virulence, alongside changes to antigenicity. Similar concerns about vaccine efficacy have been raised. Notable mutations also include K417N, E484K and N501Y.
  • Delta: Lineage B.1.617.2 emerged in India in October 2020. There is also evidence of increased transmissibility and changes to antigenicity.
  • Omicron: Lineage B.1.1.529 emerged in Botswana in November 2021.

Other notable variants include 6 other WHO-designated variants under investigation and Cluster 5, which emerged among mink in Denmark and resulted in a mink euthanasia campaign rendering it virtually extinct.

Virology

Structure

Figure of a spherical SARSr-CoV virion showing locations of structural proteins forming the viral envelope and the inner nucleocapsid
Structure of a SARSr-CoV virion

Each SARS-CoV-2 virion is 60–140 nanometres (2.4×10−6–5.5×10−6 in) in diameter; its mass within the global human populace has been estimated as being between 0.1 and 10 kilograms. Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope. Coronavirus S proteins are glycoproteins and also type I membrane proteins (membranes containing a single transmembrane domain oriented on the extracellular side). They are divided into two functional parts (S1 and S2). In SARS-CoV-2, the spike protein, which has been imaged at the atomic level using cryogenic electron microscopy, is the protein responsible for allowing the virus to attach to and fuse with the membrane of a host cell; specifically, its S1 subunit catalyzes attachment, the S2 subunit fusion.

SARS‑CoV‑2 spike homotrimer focusing upon one protein subunit with an ACE2 binding domain highlighted
SARS‑CoV‑2 spike homotrimer with one protein subunit highlighted. The ACE2 binding domain is magenta.

Genome

As of early 2022, about 7 million SARS-CoV-2 genomes had been sequenced and deposited into public databases and another 800,000 or so were added each month.

SARS-CoV-2 has a linear, positive-sense, single-stranded RNA genome about 30,000 bases long. Its genome has a bias against cytosine (C) and guanine (G) nucleotides, like other coronaviruses. The genome has the highest composition of U (32.2%), followed by A (29.9%), and a similar composition of G (19.6%) and C (18.3%). The nucleotide bias arises from the mutation of guanines and cytosines to adenosines and uracils, respectively. The mutation of CG dinucleotides is thought to arise to avoid the zinc finger antiviral protein related defense mechanism of cells, and to lower the energy to unbind the genome during replication and translation (adenosine and uracil base pair via two hydrogen bonds, cytosine and guanine via three). The depletion of CG dinucleotides in its genome has led the virus to have a noticeable codon usage bias. For instance, arginine's six different codons have a relative synonymous codon usage of AGA (2.67), CGU (1.46), AGG (.81), CGC (.58), CGA (.29), and CGG (.19). A similar codon usage bias trend is seen in other SARS–related coronaviruses.

Replication cycle

Virus infections start when viral particles bind to host surface cellular receptors. Protein modeling experiments on the spike protein of the virus soon suggested that SARS‑CoV‑2 has sufficient affinity to the receptor angiotensin converting enzyme 2 (ACE2) on human cells to use them as a mechanism of cell entry. By 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS‑CoV‑2. Studies have shown that SARS‑CoV‑2 has a higher affinity to human ACE2 than the original SARS virus. SARS‑CoV‑2 may also use basigin to assist in cell entry.

Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS‑CoV‑2. The host protein neuropilin 1 (NRP1) may aid the virus in host cell entry using ACE2. After a SARS‑CoV‑2 virion attaches to a target cell, the cell's TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide in the S2 subunit, and the host receptor ACE2. After fusion, an endosome forms around the virion, separating it from the rest of the host cell. The virion escapes when the pH of the endosome drops or when cathepsin, a host cysteine protease, cleaves it. The virion then releases RNA into the cell and forces the cell to produce and disseminate copies of the virus, which infect more cells.

SARS‑CoV‑2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response. Whether they include downregulation of ACE2, as seen in similar coronaviruses, remains under investigation (as of May 2020).

SARS-CoV-2 emerging from a human cell
SARS-CoV-2 virions emerging from a human cell
Digitally colourised scanning electron micrographs of SARS-CoV-2 virions (yellow) emerging from human cells cultured in a laboratory

Treatment and drug development

Very few drugs are known to effectively inhibit SARS‑CoV‑2. Masitinib is a clinically safe drug and was recently found to inhibit its main protease, 3CLpro and showed >200-fold reduction in viral titers in the lungs and nose in mice. However, it is not approved for the treatment of COVID-19 in humans as of August 2021. In December 2021, the United States granted emergency use authorization to Nirmatrelvir/ritonavir for the treatment of the virus; the European Union, United Kingdom, and Canada followed suit with full authorization soon after. One study found that Nirmatrelvir/ritonavir reduced the risk of hospitalization and death by 88%.

COVID Moonshot is an international collaborative open-science project started in March 2020 with the goal of developing an un-patented oral antiviral drug for treatment of SARS-CoV-2.

Epidemiology

Retrospective tests collected within the Chinese surveillance system revealed no clear indication of substantial unrecognized circulation of SARS‑CoV‑2 in Wuhan during the latter part of 2019.

A meta-analysis from November 2020 estimated the basic reproduction number () of the virus to be between 2.39 and 3.44. This means each infection from the virus is expected to result in 2.39 to 3.44 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships. Human behavior affects the R0 value and hence estimates of R0 differ between different countries, cultures, and social norms. For instance, one study found relatively low R0 (~3.5) in Sweden, Belgium and the Netherlands, while Spain and the US had significantly higher R0 values (5.9 to 6.4, respectively).

There have been about 96,000 confirmed cases of infection in mainland China. While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear, one mathematical model estimated that 75,815 people were infected on 25 January 2020 in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015. Before 24 February 2020, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province, where Wuhan is located. As of 10 March 2023, the percentage had decreased to 0.047%.

As of 10 March 2023, there have been 676,609,955 total confirmed cases of SARS‑CoV‑2 infection in the ongoing pandemic. The total number of deaths attributed to the virus is 6,881,955.

Probabilistic programming

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Probabilistic_programming   ...