COVID-19 pandemic – Wikipedia

Posted: June 30, 2022 at 9:04 pm

The COVID-19 pandemic, also known as the coronavirus pandemic, is a global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identified from an outbreak in Wuhan, China, in December 2019. Attempts to contain it there failed, allowing the virus to spread worldwide. The World Health Organization (WHO) declared a Public Health Emergency of International Concern on 30 January 2020 and a pandemic on 11 March 2020. As of 30 June 2022, the pandemic had caused more than 547million cases and 6.33million confirmed deaths, making it one of the deadliest in history.

COVID-19 symptoms range from undetectable to deadly, but most commonly include fever, dry cough, and fatigue. Severe illness is more likely in elderly patients and those with certain underlying medical conditions. COVID-19 transmits when people breathe in air contaminated by droplets and small airborne particles containing the virus. The risk of breathing these in is highest when people are in close proximity, but they can be inhaled over longer distances, particularly indoors. Transmission can also occur if contaminated fluids reach the eyes, nose or mouth, and, rarely, via contaminated surfaces. Infected persons are typically contagious for 10 days, and can spread the virus even if they do not develop symptoms. Mutations have produced many strains (variants) with varying degrees of infectivity and virulence.[5][6]

COVID-19 vaccines have been approved and widely distributed in various countries since December 2020. Other recommended preventive measures include social distancing, wearing masks, improving ventilation and air filtration, and quarantining those who have been exposed or are symptomatic. Treatments include monoclonal antibodies,[7] novel antiviral drugs, and symptom control. Governmental interventions include travel restrictions, lockdowns, business restrictions and closures, workplace hazard controls, quarantines, testing systems, and tracing contacts of the infected.

The pandemic triggered severe social and economic disruption around the world, including the largest global recession since the Great Depression.[8] Widespread supply shortages, including food shortages, were caused by supply chain disruption. The resultant near-global lockdowns saw an unprecedented pollution decrease. Educational institutions and public areas were partially or fully closed in many jurisdictions, and many events were cancelled or postponed. Misinformation circulated through social media and mass media, and political tensions intensified. The pandemic raised issues of racial and geographic discrimination, health equity, and the balance between public health imperatives and individual rights.

The pandemic is known by several names. It is often referred to in news media as the "coronavirus pandemic"[9] despite the existence of other human coronaviruses that have caused epidemics and outbreaks (e.g. SARS).[10]

During the initial outbreak in Wuhan, the virus and disease were commonly referred to as "coronavirus", "Wuhan coronavirus",[11] "the coronavirus outbreak" and the "Wuhan coronavirus outbreak",[12] with the disease sometimes called "Wuhan pneumonia".[13][14] In January 2020, the WHO recommended 2019-nCoV[15] and 2019-nCoV acute respiratory disease[16] as interim names for the virus and disease per 2015 international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma.[17] WHO finalized the official names COVID-19 and SARS-CoV-2 on 11 February 2020.[18] Tedros Adhanom explained: COfor corona, VIfor virus, Dfor disease and 19 for when the outbreak was first identified (31 December 2019).[19] WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.[18]

WHO names variants of concern and variants of interest using Greek letters. The initial practice of naming them according to where the variants were identified (e.g. Delta began as the "Indian variant") is no longer common.[20] A more systematic naming scheme reflects the variant's PANGO lineage (e.g., Omicron's lineage is B.1.1.529) and is used for other variants.[21][22][23]

SARS-CoV-2 is a newly discovered virus that is closely related to bat coronaviruses,[24] pangolin coronaviruses,[25][26] and SARS-CoV.[27] The first known outbreak started in Wuhan, Hubei, China, in November 2019. Many early cases were linked to people who had visited the Huanan Seafood Wholesale Market there,[28][29][30] but it is possible that human-to-human transmission began earlier.[31][32]

The scientific consensus is that the virus is most likely of zoonotic origin, from bats or another closely-related mammal.[31][33][34] Despite this, the subject has generated extensive speculation about alternative origins.[35][32][36] The origin controversy heightened geopolitical divisions, notably between the United States and China.[37]

The earliest known infected person fell ill on 1December 2019. That individual did not have a connection with the later wet market cluster.[38][39] However, an earlier case may have occurred on 17 November.[40] Two-thirds of the initial case cluster were linked with the market.[41][42][43] Molecular clock analysis suggests that the index case is likely to have been infected between mid-October and mid-November 2019.[44][45]

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Official "case" counts refer to the number of people who have been tested for COVID-19 and whose test has been confirmed positive according to official protocols whether or not they experienced symptomatic disease.[46][47] Due to the effect of sampling bias, studies which obtain a more accurate number by extrapolating from a random sample have consistently found that total infections considerably exceed the reported case counts.[48][49] Many countries, early on, had official policies to not test those with only mild symptoms.[50][51] The strongest risk factors for severe illness are obesity, complications of diabetes, anxiety disorders, and the total number of conditions.[52]

In early 2020, a meta-analysis of self-reported cases in China by age indicated that a relatively low proportion of cases occurred in individuals under 20.[53] It was not clear whether this was because young people were less likely to be infected, or less likely to develop symptoms and be tested.[54] A retrospective cohort study in China found that children and adults were just as likely to be infected.[55]

Among more thorough studies, preliminary results from 9 April 2020 found that in Gangelt, the centre of a major infection cluster in Germany, 15 per cent of a population sample tested positive for antibodies.[56] Screening for COVID-19 in pregnant women in New York City, and blood donors in the Netherlands, found rates of positive antibody tests that indicated more infections than reported.[57][58] Seroprevalence-based estimates are conservative as some studies show that persons with mild symptoms do not have detectable antibodies.[59]

Initial estimates of the basic reproduction number (R0) for COVID-19 in January were between 1.4 and 2.5,[60] but a subsequent analysis claimed that it may be about 5.7 (with a 95 per cent confidence interval of 3.8 to 8.9).[61]

In December 2021, the number of cases continued to climb due to several factors, including new COVID-19 variants. As of that 28December, 282,790,822 individuals worldwide had been confirmed as infected.[62] As of 14April2022[update], over 500million cases were confirmed globally.[63] Most cases are unconfirmed, with the Institute for Health Metrics and Evaluation estimating the true number of cases as of early 2022 to be in the billions.[64][65]

Semi-log plot of weekly new cases of COVID-19 in the world and the current top six countries (mean with deaths)

Total COVID-19 cases per 100,000 people from selected countries[66]

Active COVID-19 cases per 100,000 people from selected countries[66]

As of 30 June 2022, more than 6.33million[3] deaths had been attributed to COVID-19. The first confirmed death was in Wuhan on 9 January 2020.[67] These numbers vary by region and over time, influenced by testing volume, healthcare system quality, treatment options, government response,[68] time since the initial outbreak, and population characteristics, such as age, sex, and overall health.[69]

Multiple measures are used to quantify mortality.[70] Official death counts typically include people who died after testing positive. Such counts exclude deaths without a test.[71] Conversely, deaths of people who died from underlying conditions following a positive test may be included.[72] Countries such as Belgium include deaths from suspected cases, including those without a test, thereby increasing counts.[73]

Official death counts have been claimed to underreport the actual death toll, because excess mortality (the number of deaths in a period compared to a long-term average) data show an increase in deaths that is not explained by COVID-19 deaths alone.[74] Using such data, estimates of the true number of deaths from COVID-19 worldwide have included a range from 9.5 to 18.6million by The Economist,[74] as well as over 10.3million by the Institute for Health Metrics and Evaluation[75] and ~18.2million (earlier) deaths between 1 January 2020, and 31 December 2021 by a comprehensive international study.[76] Such deaths include deaths due to healthcare capacity constraints and priorities, as well as reluctance to seek care (to avoid possible infection).[77] Further research may help distinguish the proportions directly caused by COVID-19 from those caused by indirect consequences of the pandemic.[76] In May 2022, the WHO estimated the number of excess deaths to be 14.9million compared to 5.4million reported COVID-19 deaths, with the majority of the unreported 9.5million deaths believed to be direct deaths due the virus, rather than indirect deaths. Some deaths were because people with other conditions could not access medical services.[78]

The time between symptom onset and death ranges from6 to 41 days, typically about 14 days.[79] Mortality rates increase as a function of age. People at the greatest mortality risk are the elderly and those with underlying conditions.[80][81]

Semi-log plot of weekly deaths due to COVID-19 in the world and top six current countries (mean with cases)

COVID-19 deaths per 100 000 population from selected countries[66]

In May 2022 the World Health Organization estimated that COVID has caused just under 15 million excess deaths worldwide. The virus directly caused most of these deaths but some were because people with other conditions could not access medical services.[82]

The infection fatality ratio (IFR) is the cumulative number of deaths attributed to the disease divided by the cumulative number of infected individuals (including asymptomatic and undiagnosed infections and excluding vaccinated infected individuals).[84][85][86] It is expressed in percentage points (not as a decimal).[87] Other studies refer to this metric as the 'infection fatality risk'.[88][89]

In November 2020, a review article in Nature reported estimates of population-weighted IFRs for various countries, excluding deaths in elderly care facilities, and found a median range of 0.24% to 1.49%.[90]

IFRs rise as a function of age (from 0.002% at age 10 and 0.01% at age 25, to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85). These rates vary by a factor of ~10,000 across the age groups.[83] For comparison, the IFR for middle-aged adults is two orders of magnitude more likely than the annualised risk of a fatal automobile accident and far more dangerous than seasonal influenza.[83]

In December 2020, a systematic review and meta-analysis estimated that population-weighted IFR was 0.5% to 1% in some countries (France, Netherlands, New Zealand, and Portugal), 1% to 2% in other countries (Australia, England, Lithuania, and Spain), and about 2.5% in Italy. This study reported that most of the differences reflected corresponding differences in the population's age structure and the age-specific pattern of infections.[83]

Another metric in assessing death rate is the case fatality ratio (CFR),[a] which is the ratio of deaths to diagnoses. This metric can be misleading because of the delay between symptom onset and death and because testing focuses on symptomatic individuals.[91]

Based on Johns Hopkins University statistics, the global CFR is 1.16percent (6,335,512 deaths for 547,218,845 cases) as of 30 June 2022.[3] The number varies by region and has generally declined over time.[92]

Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness.[93][94] Common symptoms include headache, loss of smell and taste, nasal congestion and runny nose, cough, muscle pain, sore throat, fever, diarrhoea, and breathing difficulties.[95] People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhoea.[66] In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of cases.[96][97][98]

The disease is mainly transmitted via the respiratory route when people inhale droplets and small airborne particles (that form an aerosol) that infected people exhale as they breathe, talk, cough, sneeze, or sing.[99][100][101][102] Infected people are more likely to transmit COVID-19 when they are physically close. However, infection can occur over longer distances, particularly indoors.[99][103]

SARSCoV2 belongs to the broad family of viruses known as coronaviruses.[104] 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.[105] 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.[106]

The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests,[107] which detects the presence of viral RNA fragments.[108] As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited."[109] The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used.[110][111] The WHO has published several testing protocols for the disease.[112]

Preventive measures to reduce the chances of infection include getting vaccinated, staying at home, wearing a mask in public,[113] avoiding crowded places, keeping distance from others, ventilating indoor spaces, managing potential exposure durations,[114] washing hands with soap and water often and for at least twenty seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.[115][116]

Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.[117][118]

A COVID-19 vaccine is intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARSCoV2), the virus that causes coronavirus disease 2019 (COVID-19). Prior to the COVID-19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020.[119] The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness.[120] On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.[121] The COVID-19 vaccines are widely credited for their role in reducing the severity and death caused by COVID-19.[122][123]

As of late-December 2021, more than 4.49billion people had received one or more doses[124] (8+ billion in total) in over 197 countries. The Oxford-AstraZeneca vaccine was the most widely used.[125]

For the first two years of the pandemic, no specific and effective treatment or cure was available.[126][127] In 2021, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) approved the oral antiviral protease inhibitor, Paxlovid (nirmatrelvir plus AIDS drug ritonavir), to treat adult patients.[128] FDA later gave it an EUA.[129]

Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever,[130] body aches, cough), adequate intake of oral fluids and rest.[127][131] Good personal hygiene and a healthy diet are also recommended.[132]

Supportive care includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning, and medications or devices to support other affected vital organs.[133] More severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is recommended, to reduce mortality.[134] Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing.[135] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure.[136][137]

Existing drugs such as hydroxychloroquine, lopinavir/ritonavir, ivermectin and so-called early treatment are not recommended by US or European health authorities.[126][138][139] Two monoclonal antibody-based therapies are available for early use in high-risk cases.[139] The antiviral remdesivir is available in the US, Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for use with mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO),[140] due to limited evidence of its efficacy.[126]

Several variants have been named by WHO and labelled as a variant of concern (VoC) or a variant of interest (VoI). They share the more infectious D614G mutation:[141][142][143] Delta dominated and then eliminated earlier VoC from most jurisdictions. Omicron's immune escape ability may allow it to spread via breakthrough infections, which in turn may allow it to coexist with Delta, which more often infects the unvaccinated.[144]

The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 34% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization.[146] Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to intensive care units (ICU).[147][148]

Many countries attempted to slow or stop the spread of COVID-19 by recommending, mandating or prohibiting behaviour changes, while others relied primarily on providing information. Measures ranged from public advisories to stringent lockdowns. Outbreak control strategies are divided into elimination and mitigation. Experts differentiate between elimination strategies (commonly known as "zero-COVID") that aim to completely stop the spread of the virus within the community,[152] and mitigation strategies (commonly known as "flattening the curve") that attempt to lessen the effects of the virus on society, but which still tolerate some level of transmission within the community.[153] These initial strategies can be pursued sequentially or simultaneously during the acquired immunity phase through natural and vaccine-induced immunity.[154]

Nature reported in 2021 that 90 per cent of immunologists who responded to a survey "think that the coronavirus will become endemic".[155]

Containment is undertaken to stop an outbreak from spreading into the general population. Infected individuals are isolated while they are infectious. The people they have interacted with are contacted and isolated for long enough to ensure that they are either not infected or no longer contagious. Screening is the starting point for containment. Screening is done by checking for symptoms to identify infected individuals, who can then be isolated or offered treatment.[156] The Zero-COVID strategy involves using public health measures such as contact tracing, mass testing, border quarantine, lockdowns and mitigation software to stop community transmission of COVID-19 as soon as it is detected, with the goal of getting the area back to zero detected infections and resuming normal economic and social activities.[152][157] Successful containment or suppression reduces Rt to less than 1.[158]

Should containment fail, efforts focus on mitigation: measures taken to slow the spread and limit its effects on the healthcare system and society.Successful mitigation delays and decreases the epidemic peak, known as "flattening the epidemic curve".[149] This decreases the risk of overwhelming health services and provides more time for developing vaccines and treatments.[149]

Individual behaviour changed in many jurisdictions. Many people worked from home instead of at their traditional workplaces.[159]

Non-pharmaceutical interventions that may reduce spread include personal actions such as hand hygiene, wearing face masks, and self-quarantine; community measures aimed at reducing interpersonal contacts such as closing workplaces and schools and cancelling large gatherings; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such as surface cleaning. Many such measures were criticised as hygiene theatre.[161]

More drastic actions, such as quarantining entire populations and strict travel bans have been attempted in various jurisdictions.[162] China and Australia's lockdowns have been the most strict. New Zealand implemented the most severe travel restrictions. South Korea introduced mass screening and localised quarantines, and issued alerts on the movements of infected individuals. Singapore provided financial support, quarantined, and imposed large fines for those who broke quarantine.[163]

Contact tracing attempts to identify recent contacts of newly infected individuals, and to screen them for infection;[164] the traditional approach is to request a list of contacts from infectees, and then telephone or visit the contacts.

Another approach is to collect location data from mobile devices to identify those who have come in significant contact with infectees, which prompted privacy concerns.[165] On 10 April 2020, Google and Apple announced an initiative for privacy-preserving contact tracing.[166][167] In Europe and in the US, Palantir Technologies initially provided COVID-19 tracking services.[168]

WHO described increasing capacity and adapting healthcare as a fundamental mitigation.[169] The ECDC and WHO's European regional office issued guidelines for hospitals and primary healthcare services for shifting resources at multiple levels, including focusing laboratory services towards testing, cancelling elective procedures, separating and isolating patients, and increasing intensive care capabilities by training personnel and increasing ventilators and beds.[169][170] The pandemic drove widespread adoption of telehealth.[171]

Due to capacity supply chains limitations, some manufacturers began 3D printing material such as nasal swabs and ventilator parts.[172][173] In one example, an Italian startup received legal threats due to alleged patent infringement after reverse-engineering and printing one hundred requested ventilator valves overnight.[174] On 23 April 2020, NASA reported building, in 37 days, a ventilator which is undergoing further testing.[175][176] Individuals and groups of makers created and shared open source designs, and manufacturing devices using locally sourced materials, sewing, and 3D printing. Millions of face shields, protective gowns, and masks were made. Other ad hoc medical supplies included shoe covers, surgical caps, powered air-purifying respirators, and hand sanitizer. Novel devices were created such as ear savers, non-invasive ventilation helmets, and ventilator splitters.[177]

In July 2021, several experts expressed concern that achieving herd immunity may not be possible because Delta can transmit among vaccinated individuals.[178] CDC published data showing that vaccinated people could transmit Delta, something officials believed was less likely with other variants. Consequently, WHO and CDC encouraged vaccinated people to continue with non-pharmaceutical interventions such as masking, social distancing, and quarantining if exposed.[179]

In February 2022, the Icelandic Ministry of Health lifted all restrictions and adopted a herd immunity approach,[180] and in June 2022 the Icelandic Ministry of Health's chief epidemiologist rlfur Gunason said that "we have acquired a good herd immunity, because otherwise the situation would be much worse."[181]

The outbreak was discovered in Wuhan in November 2019. It is possible that human-to-human transmission was happening before the discovery.[31][32] Based on a retrospective analysis starting from December 2019, the number of cases in Hubei gradually increased, reaching 60 by 20 December and at least 266 by 31 December.[183]

A pneumonia cluster was observed on 26 December and treated by Doctor Zhang Jixian. She informed the Wuhan Jianghan CDC on 27 December.[184] Vision Medicals reported the discovery of a novel coronavirus to the China CDC (CCDC) on 28 December.[185][186]

On 30 December, a test report from CapitalBio Medlab addressed to Wuhan Central Hospital reported an erroneous positive result for SARS, causing doctors there to alert authorities. Eight of those doctors, including Li Wenliang (who was also punished on 3January),[187] were later admonished by the police for spreading false rumours; and Ai Fen was reprimanded.[188] That evening, Wuhan Municipal Health Commission (WMHC) issued a notice about "the treatment of pneumonia of unknown cause".[189] The next day, WMHC made the announcement public, confirming 27 cases[190][191][192]enough to trigger an investigation.[193]

On 31 December, the WHO office in China was informed of cases of the pneumonia cases[194][190] and immediately launched an investigation.[193]

Official Chinese sources claimed that the early cases were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals.[195] However, in May 2020, CCDC director George Gao indicated the market was not the origin (animal samples had tested negative).[196]

On 11 January, WHO was notified by the Chinese National Health Commission that the outbreak was associated with exposures in the market, and that China had identified a new type of coronavirus, which it isolated on 7 January.[194]

Initially, the number of cases doubled approximately every seven and a half days.[197] In early and mid-January, the virus spread to other Chinese provinces, helped by the Chinese New Year migration. Wuhan was a transport hub and major rail interchange.[198] On 10 January, the virus's genome was shared through GISAID.[199] A retrospective study published in March found that 6,174 people had reported symptoms by 20 January.[200] A 24 January report indicated human transmission, recommended personal protective equipment for health workers, and advocated testing, given the outbreak's "pandemic potential".[41][201] On 31 January the first published modelling study warned of inevitable "independent self-sustaining outbreaks in major cities globally" and called for "large-scale public health interventions."[202]

On 30 January, 7,818 infections had been confirmed, leading WHO to declare the outbreak a Public Health Emergency of International Concern (PHEIC).[203][204] On 11 March, WHO elevated it to a pandemic.[205][206]

By 31 January, Italy had its first confirmed infections, in two tourists from China.[207] On 19 March, Italy overtook China as the country with the most reported deaths.[208] By 26 March, the United States had overtaken China and Italy as the country with the highest number of confirmed infections.[209] Genomic analysis indicated that the majority of New York's confirmed infections came from Europe, rather than directly from Asia.[210] Testing of prior samples revealed a person who was infected in France on 27 December 2019[211][212] and a person in the United States who died from the disease on 6February.[213]

In April Russia sent a cargo plane with medical aid to the United States.[214]

In October, WHO reported that one in ten people around the world may have been infected, or 780million people, while only 35million infections had been confirmed.[215]

On 9 November, Pfizer released trial results for a candidate vaccine, showing a 90 per cent effectiveness against infection.[216] That day, Novavax entered an FDA Fast Track application for their vaccine.[217]

On 14 December, Public Health England reported that a variant had been discovered in the UK's southeast, predominantly in Kent. The variant, later named Alpha, showed changes to the spike protein that could be more infectious. As of 13 December, 1,108 infections had been confirmed.[218]

On 4 February 2020, US Secretary of Health and Human Services Alex Azar waived liability for vaccine manufacturers.[219]

On 2 January, the Alpha variant, first discovered in the UK, had been identified in 33 countries.[220] On 6 January, the Gamma variant was first identified in Japanese travellers returning from Brazil.[221] On 29 January, it was reported that the Novavax vaccine was 49 per cent effective against the Beta variant in a clinical trial in South Africa.[222][223] The CoronaVac vaccine was reported to be 50.4 per cent effective in a Brazil clinical trial.[224]

On 12 March, several countries stopped using the Oxford-AstraZeneca COVID-19 vaccine due to blood clotting problems, specifically cerebral venous sinus thrombosis (CVST).[225] On 20 March, the WHO and European Medicines Agency found no link to thrombus, leading several countries to resume the vaccine.[226] In March WHO reported that an animal host was the most likely origin, without ruling out other possibilities.[2][30] The Delta variant was first identified in India. In mid-April, the variant was first detected in the UK and two months later it had metastasized into a third wave there, forcing the government to delay reopening that was originally scheduled for June.[227]

On 10 November, Germany advised against the Moderna vaccine for people under 30.[228] On 24 November, the Omicron variant was detected in South Africa; a few days later the World Health Organization declared it a VoC (variant of concern).[229] The new variant is more infectious than the Delta variant.[230]

On 1 January, Europe passed 100 million cases amidst a surge in the Omicron variant.[231]

On 14 January, the World Health Organization recommended two new treatments, Baricitinib, and Sotrovimab (although conditionally).[232]

On 24 January, it was reported that about 57% of the world had been infected by COVID-19, per the Institute for Health Metrics and Evaluation Model.[64][65]

On 6 March, it was reported that the total worldwide death count had surpassed 6million people since the start of the pandemic.[233]

National reactions ranged from strict lockdowns to public education campaigns.[234] WHO recommended that curfews and lockdowns should be short-term measures to reorganise, regroup, rebalance resources, and protect the health care system.[235]As of 26 March 2020, 1.7billion people worldwide were under some form of lockdown.[236] This increased to 3.9billion people by the first week of Aprilmore than half the world's population.[237][238]

As of the end of 2021, Asia's peak had come at the same time and at the same level as the world as a whole, in May 2021.[239] However, cumulatively they had experienced only half the world average.[240]

China opted for containment, inflicting strict lockdowns to eliminate spread.[241][242]The vaccines distributed in China included the BIBP, WIBP, and CoronaVac.[243] It was reported on 11 December 2021 that China had vaccinated 1.162billion of its citizens, or 82.5% of the total population of the country against COVID-19.[244] During the initial outbreak, multiple sources cast doubt upon the accuracy of China's death tolls, with some suggesting intentional data suppression.[245][246][247] China's large scale adoption of Zero-COVID had largely contained the first wave of infections of the disease, with external experts agreeing with the accuracy of China's infection numbers and deaths since the initial outbreak.[248][249][250] China is almost alone in pursuing a Zero-Covid policy to combat the continuing wave of infections due to the Omicron variant in 2022.[251]

The first case in India was reported on 30 January 2020. India ordered a nationwide lockdown starting 24 March 2020,[252] with a phased unlock beginning 1 June 2020. Six cities accounted for around half of reported casesMumbai, Delhi, Ahmedabad, Chennai, Pune and Kolkata.[253] Post-lockdown, the Government of India introduced a contact tracking app called Arogya Setu to help authorities manage contact tracing. Later this app was also used for a vaccination management program.[254] India's vaccination program was considered to be the world's largest and the most successful with over 90% of citizens getting the first dose and another 65% getting the second dose.[255][256] A second wave hit India in April 2021, straining healthcare services.[257] On 21 October 2021, it was reported that the country had surpassed 1billion vaccinations.[258]

Iran reported its first confirmed cases on 19 February 2020 in Qom.[260][261] Early measures included the cancellation of concerts and other cultural events,[262] Friday prayers,[263] and education shutdowns.[264] Iran became a centre of the pandemic in February 2020.[265][266] More than ten countries had traced their outbreaks to Iran by 28 February, indicating a more severe outbreak than the 388 reported cases.[266][267] The Iranian Parliament closed, after 23 of its 290 members tested positive on 3March 2020.[268] At least twelve sitting or former Iranian politicians and government officials had died by 17 March 2020.[269] By August 2021, the pandemic's fifth wave peaked, with more than 400 deaths in 1 day.[270]

COVID-19 was confirmed in South Korea on 20 January 2020. Military bases were quarantined after tests showed three infected soldiers.[271] South Korea introduced what was then considered the world's largest and best-organised screening programme, isolating infected people, and tracing and quarantining contacts.[272] Screening methods included mandatory self-reporting by new international arrivals through mobile application,[273] combined with drive-through testing,[274] and increasing testing capability to 20,000 people/day.[275] Despite some early criticisms,[276] South Korea's programme was considered a success in controlling the outbreak without quarantining entire cities.[272][277][278]

The global COVID-19 pandemic arrived in Europe with its first confirmed case in Bordeaux, France, on 24 January 2020, and subsequently spread widely across the continent. By 17 March 2020, every country in Europe had confirmed a case,[279] and all have reported at least one death, with the exception of Vatican City. Italy was the first European nation to experience a major outbreak in early 2020, becoming the first country worldwide to introduce a national lockdown.[280] By 13 March 2020, the World Health Organization (WHO) declared Europe the epicentre of the pandemic[281][282] and it remained so until the WHO announced it has been overtaken by South America on 22 May.[283] By 18 March 2020, more than 250million people were in lockdown in Europe.[284] Despite deployment of COVID-19 vaccines, Europe became the pandemic's epicentre once again in late 2021.[285][286]

The Italian outbreak began on 31 January 2020, when two Chinese tourists tested positive for SARS-CoV-2 in Rome.[207] Cases began to rise sharply, which prompted the government to suspend flights to and from China and declare a state of emergency.[287] On 22 February 2020, the Council of Ministers announced a new decree-law to contain the outbreak, including quarantining more than 50,000 people in northern Italy.[288] On 4 March the Italian government ordered schools and universities closed as Italy reached a hundred deaths. Sport was suspended completely for at least one month.[289] On 11 March Conte stopped nearly all commercial activity except supermarkets and pharmacies.[290][291] On 19 March Italy overtook China as the country with the most COVID-19-related deaths.[292][293] On 19 April the first wave ebbed, as 7-day deaths declined to 433.[294] On 13 October, the Italian government again issued restrictive rules to contain the second wave.[295] On 10 November Italy surpassed 1million confirmed infections.[296] On 23 November, it was reported that the second wave of the virus had led some hospitals to stop accepting patients.[297]

The virus was first confirmed to have spread to Spain on 31 January 2020, when a German tourist tested positive for SARS-CoV-2 in La Gomera, Canary Islands.[298] Post-hoc genetic analysis has shown that at least 15 strains of the virus had been imported, and community transmission began by mid-February.[299] On 29 March, it was announced that, beginning the following day, all non-essential workers were ordered to remain at home for the next 14 days.[300] The number of cases increased again in July in a number of cities including Barcelona, Zaragoza and Madrid, which led to reimposition of some restrictions but no national lockdown.[301][302][303][304] By September 2021, Spain was one of the countries with the highest per centage of its population vaccinated (76% fully vaccinated and 79% with the first dose),[305] while also being one of the countries more in favour of vaccines against COVID-19 (nearly 94% of its population were already vaccinated or wanted to be).[306] However, as of 21 January 2022, this figure had only increased to 80.6%. Nevertheless, Spain leads Europe for per-capita full-vaccination rates. Italy is ranked 2nd at 75%.[305]

Sweden differed from most other European countries in that it mostly remained open.[307] Per the Swedish Constitution, the Public Health Agency of Sweden has autonomy that prevents political interference and the agency favoured remaining open. The Swedish strategy focused on longer-term measures, based on the assumption that after lockdown the virus would resume spreading, with the same result.[308][309] By the end of June, Sweden no longer had excess mortality.[310]

Devolution in the United Kingdom meant that each of its four countries developed its own response. England's restrictions were shorter-lived than the others.[311] The UK government started enforcing social distancing and quarantine measures on 18 March 2020.[312][313] On 16 March, Prime Minister Boris Johnson advised against non-essential travel and social contact, praising work from home and avoiding venues such as pubs, restaurants, and theatres.[314][315] On 20 March, the government ordered all leisure establishments to close,[316] and promised to prevent unemployment.[317] On 23 March, Johnson banned gatherings and restricted non-essential travel and outdoor activity. Unlike previous measures, these restrictions were enforceable by police through fines and dispersal of gatherings. Most non-essential businesses were ordered to close.[318] On 24 April 2020, it was reported that a promising vaccine trial had begun in England; the government pledged more than 50million towards research.[319] On 16 April 2020, it was reported that the UK would have first access to the Oxford vaccine, due to a prior contract; should the trial be successful, some 30million doses would be available.[320] On 2 December 2020, the UK became the first developed country to approve the Pfizer vaccine; 800,000 doses were immediately available for use.[321]

The virus arrived in the United States on 13 January 2020.[322] Cases were reported in all North American countries after Saint Kitts and Nevis confirmed a case on 25 March, and in all North American territories after Bonaire confirmed a case on 16 April.[323]

87,410,874[324] confirmed cases have been reported in the United States with 1,017,467[324] deaths, the most of any country, and the nineteenth-highest per capita worldwide.[325] COVID-19 is the deadliest pandemic in U.S. history;[326] it was the third-leading cause of death in the U.S. in 2020, behind heart disease and cancer.[327] From 2019 to 2020, U.S. life expectancy dropped by 3years for Hispanic Americans, 2.9years for African Americans, and 1.2years for white Americans.[328] These effects have persisted as U.S. deaths due to COVID-19 in 2021 exceeded those in 2020.[329] In the United States, COVID-19 vaccines became available in December 2020, under emergency use, beginning the national vaccination program, with the first vaccine officially approved by the Food and Drug Administration (FDA) on 23 August 2021.[330]

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