Thread by @meder_o

What did we learn about COVID in 2020? A thread on studies from the first year.. part 1:

Firstly, to recap:

December 31, 2019: China notifies WHO of pneumonia of unknown cause
January 9, 2020: First coronavirus-related death reported in Wuhan, China
January 10, 2020: SARS-CoV-2 full genome sequence uploaded to virological dot org

January 23, 2020: Zhu et al, NEJM (lab virology) identified the virus now known as SARS-CoV-2 (then called 2019-nCoV), isolated it and sequenced the entire genome establishing the groundwork for PCR testing

January 23, 2020: Corman et al., Eurosurveillance (assay development) designed the first real-time RT-PCR test for the novel coronavirus (2019-nCoV) using publicly released genome sequences

January 24, 2020: Huang et al, Lancet (clinical case series) documented what COVID-19 looks like in 41 patients from a clinical perspective - symptoms, lab tests, xrays

Reported elevated cytokines in severe patients hinting at what is now known as a cytokine storm

January 24, 2020: Chan et al, Lancet (observational case series) documented human to human transmission and an asymptomatic infection (a child with ground-glass opacities on the CT but no symptoms)

January 29, 2020: Li et al, NEJM (modeling study) provided the first epidemiological parameters - an R0 number of 2.2 meaning each infected person would transmit the virus to at least 2 other people

February 3, 2020: Zhou et al, Nature (lab virology) identified ACE2 as the primary entry receptor (found in many parts of the body like the nose, lungs, gut, heart, and kidneys) similar to SARS-CoV-1

February 7, 2020: Wang et al, JAMA (clinical cohort) reported that 41% of COVID-19 cases in a Wuhan hospital were hospital-acquired, providing the first clear evidence of widespread nosocomial transmission

February 7, 2020: Professor Junji Cao warned Professor Lidia Morawska that the airborne transmission route of the virus may not be well recognized

February 10, 2020: Coutard et al, Antiviral Research (genomic analysis) identified a unique RRAR furin cleavage site in the SARS-CoV-2 spike protein - absent in SARS-CoV-1 - makes SARS-CoV-2 unusually infectious

February 11, 2020: Xia et al, Nature (experimental virology) proved SARS-CoV-2's spike merges with human cells far more easily than SARS-CoV-1 (on top of ACE2 / RRAR)

February 19, 2020: Wrapp et al, Nature (experimental cryo-EM) discovered SARS-CoV-2's spike protein (key) sticks to the entryway (lock/ACE2 receptor) 10-20x stronger than SARS-CoV-1

February 21, 2020: Bai et al, JAMA (case series) reported an asymptomatic person transmitting/seeding multiple infections with a comprehensive account of asymptomatic transmission

February 23, 2020: Patient 31 was identified in South Korea as the index case linked to the Shincheonji Church of Jesus in Daegu - one of the first superspreader events

February 24, 2020: Wu & McGoogan, JAMA (epidemiologic analysis) showed that outcomes worsened sharply with age and that severe cases could deteriorate rapidly by reviewing 72,314 cases from China

February 28, 2020: Guan et al, NEJM (multicenter cohort) revealed what COVID-19 actually looks like: many patients arrived without fever, some progressed to severe illness, blood counts were often abnormal, and lung damage appeared on CT even when symptoms were mild

March 3, 2020: Wang et al., J Hosp Infect (observational) hinted healthcare workers using N95 respirators were far less likely to be infected

March 5, 2020: Hoffman et al, Cell (cell-entry mechanistic) showed that after binding ACE2, SARS-CoV-2 relies mainly on the lung enzyme TMPRSS2 to activate its spike for cell-surface fusion but can also use a backup endosomal route via cathepsins

March 11, 2020: Zhou et al, Lancet (retrospective cohort) traced the clinical course of hospitalized COVID-19 patients, revealing severe COVID is a systemic, life-threatening ilness, not just a lung infection

March 11, 2020: WHO Declares a global pandemic
March 13, 2020: US declares a national emergency

March 16, 2020: Li et al, Science (epidemiological modeling) found that ~86% of SARS-CoV-2 infections were undocumented before travel restrictions were put in place and these unseen cases drove most early spread

March 17, 2020: Zheng et al, Nature (clinical immunology) found that severe COVID-19 is marked by T-cell exhaustion, suggesting immune dysfunction

March 17, 2020: Doremalen et al, NEJM (experimental) showed SARS-CoV-2 remains viable in aerosols for hours, supporting airborne spread. Also noted surface (fomite) transmission was plausible

March 19, 2020: Zou et al, NEJM (virology observational) showed that SARS-CoV-2 reaches extremely high viral loads in the nose and throat at or before symptom onset which explained the ease of presymptomatic transmission and why COVID-19 spreads so efficiently through shared air.

March 26, 2020: Giacomelli et al, Clinical Infectious Diseases (cross-sectional observational) found that a large share of hospitalized patients reported loss of smell and/or taste, helping establish anosmia and ageusia as early symptoms of infection

March 26, 2020: Bourouiba et al, JAMA (mechanistic) highlighted that SARS-CoV-2 can spread much farther than current social distancing guidelines suggest (far past the social distance recommendation of 6 ft, up to ~23-27 ft), especially indoors

March 27, 2020: Chen et al, Journal of Clinical Investigation (retrospective clinical) compared severe vs moderate cases and found severe disease linked to lympophenia (lower CD4/CD8 t-cells) and higher inflammatory markers (IL-2R, IL-6/IL-10, TNF-a, ferritin, D-dimer)

March 28, 2020: Mehta et al, Lancet (commentary) introduced the idea that severe COVID-19 can involve a cytokine storm and proposed immunosuppression (e.g., IL-6 inhibitors) as a potential treatment

April 1, 2020: Wölfel et al., Nature (clinical virology) demonstrated that the virus replicates first in the nose and throat rather than the lungs, helping explain early airborne spread

April 1, 2020: Zhao et al., Lancet (case report) documented the first case of Guillain-Barré syndrome associated with COVID-19

April 2, 2020: Sriwijitalai and Wiwanitkit, American Journal of Otolaryngology (report) documented a case of hearing loss after an infection

April 2, 2020: Lu et al., Emerging Infectious Diseases (outbreak investigation) found COVID-19 spread between diners seated ~1 m apart only along AC airflow, inconsistent with simple droplet spread alone. Evidence that airflow-borne respiratory particles drive indoor transmission

April 8, 2020: Shi et al, Science (experimental) showed that cats are susceptible to airborne transmission from SARS-CoV-2

April 10, 2020: Mao et al., JAMA (observational case series) showcased evidence of neurological implications from COVID-19. In 214 patients over 1 in 3 had neurological symptoms

April 10, 2020: Klok et al., Thrombosis Research (observational cohort) found a striking 31% rate of thrombotic complications, mostly blood clots (PE/DVT), despite standard prophylaxis in COVID-19 ICU patients

April 10, 2020: Lidia Morawska and Junji Cao Environment International (commentary) warned that COVID-19 spreads through the air, arguing that aerosols can travel meters indoors and urging ventilation and masking.

April 10, 2020: Sungnak et al., Nature (single-cell RNA-seq atlas analysis) showed the virus grabs onto certain cells in the nose first (nasal goblet and ciliated cells), explaining why the nose is the main starting point of infection

April 13, 2020: Kim et al, European Heart Journal (case report) found myocarditis in a patient with no pre-existing conditions after a COVID-19 infection

April 14, 2020: Kissler et al., Science (epidemiological modeling) modeled COVID-19 future waves and warned it would not be one wave. With short-lived immunity, repeated surges were likely.

April 15, 2020: He et al., Nature Medicine (viral kinetics modeling) showed that SARS-CoV-2 viral shedding peaks before symptom onset and continues for days, providing early quantitative evidence for asymptomatic and presymptomatic transmission

April 17, 2020: Packwood et al., Clinical Practice and Cases in Emergency Medicine (case report) reported one of the earliest cases of shingles post COVID

April 28, 2020: Oxley et al., NEJM (case series) reported large-vessel strokes in young COVID-19 patients, raising early concern that SARS-CoV-2 can trigger severe clotting events even without typical risk factors

May 1, 2020: Diao et al., Frontiers in Immunology (clinical immunology) showed that COVID-19 is associated with reduced and exhausted T cells, building on earlier reports of lymphopenia and helping explain immune weakening

May 2, 2020: Varga et al., Lancet (case series) showed that SARS-CoV-2 can directly infect endothelial cells lining blood vessels, causing widespread vascular inflammation (endotheliitis) and helping explain clotting, ischemia, and multi-organ complications in COVID-19

May 11, 2020: PLRC / Body Politic COVID-19 Support Group conducted a survey (640 responses) tracking 62 symptoms week by week, with 200+ more symptoms reported by patients, showing that recovery wasn’t quick, predictable, or guaranteed

May 13, 2020: Zang et al., Science Immunology (lab gut-organoid study) showed SARS-CoV-2 can infect and replicate in gut lining cells using TMPRSS2/TMPRSS4, helping explain GI symptoms

May 14, 2020: Sia et al., Nature (animal model / hamster study) showed SARS-CoV-2 spreads efficiently between hamsters through the air, becoming key evidence that inhaling a relatively small airborne dose over a short time can be enough to establish infection

May 15, 2020: Blanco-Melo et al., Cell (lab + animal + patient immune-response) found that COVID can slip past the body’s early antiviral defenses, allowing the virus to spread quietly at first, before triggering a strong inflammatory reaction later. This helped explain why COVID can linger and suddenly become severe.

May 15, 2020: Hamner et al., MMWR (CDC outbreak investigation) reported the Skagit Valley choir superspreading event, where one symptomatic singer infected ~87% of attendees in ~2.5 hours. The authors note singing increases aerosol emission, making droplet-only spread unlikely

May 18, 2020: Zhang et al., Journal of Thrombosis and Haemostasis (hospital cohort) found deep vein thrombosis in 46% of hospitalized COVID-19 patients in Wuhan, many without symptoms

May 20, 2020: Guo et al., Journal of Bone and Joint Surgery (case control study) showed orthopaedic surgeons in Wuhan were infected mainly in general wards, with higher risk when not wearing N95s and lower risk with consistent masking and infection control training

May 21, 2020: Ackermann et al., NEJM (comparative autopsy pathology study) found COVID-19 causes severe injury to the lung’s blood vessel lining, with widespread endothelial infection, 9x more microclots than influenza, and abnormal new vessel growth.

The findings showed COVID-19 can behave as a vascular disease, helping explain profound hypoxia, clotting, and multi-organ involvement

May 23, 2020: Riphagen et al., Lancet (case series): Found a small subset of children who recovered from SARS-CoV-2 infection had, what were described at the time as, severe Kawasaki disease-like symptoms 4–6 weeks after recovery from the initial infection

May 27, 2020: Morawska et al. / Group 36, Environment International (expert correspondence): A group of 36 international aerosol, indoor-air, HVAC, and infectious-disease experts warned that airborne transmission of SARS-CoV-2 indoors was being downplayed, and called for ventilation, filtration, reduced air recirculation, and other clean-air engineering controls to limit spread

May 27, 2020: Prather et al., Science (perspective) pointed out that a large share of COVID spread can happen through shared air and masking/testing are necessary to reduce cases to combat asymptomatic spread

June 2, 2020: Kanitakis et al., Journal of American Academy of Dermatology (case series) reported a case of COVID-toes, chilblain-like skin lesions on the toes

June 11, 2020: Zhang et al., PNAS (epidemiological analysis): Analyzed outbreak trends in Wuhan, Italy, and NYC and argued that airborne transmission was the dominant driver of COVID-19 spread and wearing masks as the most effective way of preventing spread

June 25, 2020: Rapkiewicz et al., Lancet (case series) showed that in people who died from COVID-19, their organs were full of tiny blood clots made mostly of platelets, and there were big cells called megakaryocytes - which usually stay in the bone marrow - showing up in places like the lungs and heart, where they don’t usually belong

July 3, 2020: Korber et al., Cell (genomic epidemiology + lab experiments) showed that a small change in the virus's spike protein (called D614G) made COVID spread more easily. That version quickly replaced earlier strains around the world, helping explain why the virus suddenly became harder to contain

July 6, 2020: Morawska & Milton, Clinical Infectious Diseases (invited commentary) a landmark consensus statement from 239 scientists across ~32 countries was submitted urging WHO and the medical community to recognize airborne transmission of SARS-CoV-2.

This pushed airborne spread into the mainstream conversation. Afterward, health agencies (WHO) slowly began updating their advice to focus more on indoor air, ventilation, and masks, with fuller acknowledgment of airborne spread coming over the following months into 2021

July 8, 2020: Paterson et al., Brain (clinical case series) showed COVID can hit the nervous system: confusion/delirium/psychosis, inflammatory brain/spinal syndromes, strokes, and peripheral nerve problems like Guillain-Barré that could show up days to weeks after infection

July 9, 2020: Carfì et al., JAMA (research letter; observational follow-up cohort): Showed that many COVID patients still had symptoms weeks after recovery, an early warning sign of what would later be called Long COVID

July 10, 2020: Gupta et al., Nature (review) highlighted that COVID-19 is more of a systemic disease than simply a respiratory/lung disease

Aug 2020: Hadjadj et al., Science (patient cohort + immune profiling) found that in severe COVID, the body’s early warning system against viruses (type-I interferons) doesn’t turn on properly. This lets the virus multiply freely at first, even when symptoms seem mild - and helps explain why some people suddenly crash days later

July 17, 2020: Liew et al., Journal of Clinical Rheumatology (case report) documented arthritis after a COVID infection

July 27, 2020: Puntmann et al., JAMA (observational cohort) found that cardiac MRI frequently showed signs of ongoing heart inflammation or tissue changes in people recently recovered from COVID - 78 of 100 participants, many previously healthy

July 29, 2020: Berrent et al. (survey) the Survivor Corps group / Indiana University documented 98 long-hauler symptoms such as hair loss which wasn't as previously reported in previous studies or polls

August 6, 2020: Bouhaddou et al., Cell (cell biology) showed that COVID-19 can force infected cells to grow long finger-like extensions (filopodia) that carry virus particles, likely helping the virus spread directly from cell to cell in a way not commonly seen with other viruses.

August 11, 2020: Mathew et al., Science (immunophenotyping cohort) showed that COVID-19 patients mount distinct immune response patterns, helping explain why outcomes vary so widely. While later work showed these immune responses shift over time rather than fitting into rigid boxes - but this study helped setup the groundwork

August 11, 2020: Tcharkhtchi et al., Bioactive Materials (review) explains proper fit and multilayered technology (interception, diffusion, electrostatic charge) that attracts particles to make N95 masks effective

August 19, 2020: Kaneko et al., Cell (human tissue study) showed that severe COVID-19 can shut down germinal centers - the immune system’s antibody "training centers." Losing them helps explain why natural infection often produces weaker, short-lived antibodies and why reinfections happen

August 25, 2020: To et al., Clinical Infectious Diseases (case report with whole-genome sequencing) confirmed the first documented COVID-19 reinfection.
A patient was infected twice by genetically distinct SARS-CoV-2 strains, proving reinfection was real and not just prolonged viral shedding

September 1, 2020: Kang et al., Annals of Internal Medicine (epidemiologic/environmental investigation) reported probable fecal aerosol transmission of SARS-CoV-2 in a high-rise building, showing virus spread between vertically aligned apartments through shared bathroom drainage pipes and highlighting toilets and plumbing as overlooked transmission routes

September 14, 2020: Edridge et al., Nature (longitudinal cohort) analyzed 35 years of archived samples to show seasonal coronavirus reinfections and antibody waning, with evidence of reinfection as early as 6 months

September 18, 2020: Choi et al., Emerging Infectious Diseases (epidemiologic investigation with viral genome sequencing) provided some of the strongest early evidence of in-flight transmission of SARS-CoV-2, showing that passengers and crew on the same long-haul flight carried genetically identical virus, confirming transmission occurred during air travel

September 24, 2020: Perego and Callard et al., Wellcome Open Research (open letter) explained why the patient-made term “Long Covid” is needed.

The term was first coined by Elisa Perego in May 2020 and helped give language and visibility to persistent, relapsing symptoms after SARS-CoV-2 infection, pushing recognition in research, care, and policy

September 24, 2020: Bastard et al., Science (human immunology study) found that about 10 percent of patients with life-threatening COVID-19 had pre-existing autoantibodies that block type I interferons, crippling the body’s early antiviral defense.

Helped explain why some people develop severe disease despite no obvious risk factors

October 15, 2020: Mathieu et al., JAAD Case Reports (case report) described new-onset pustular psoriasis appearing after COVID-19, in a patient with no prior psoriasis history.

October 26, 2020: Seow et al., Nature (longitudinal immunology study) showed that neutralizing antibodies after SARS-CoV-2 infection decline within months, especially after mild illness, helping explain reinfections and why infection alone does not guarantee lasting immunity

November 4, 2020: Buchrieser et al., EMBO Journal (lab study) showed that SARS-CoV-2 can make infected cells fuse with nearby cells into large "giant cells" called syncytia, which may help explain some lung tissue damage in severe COVID

November 12, 2020: Clausen et al., Cell (lab/cell/virus assays) found SARS-CoV-2 does not just “grab” ACE2. It also latches onto heparan sulfate, a sugar coating on our cells, which helps the spike line up with ACE2

November 15, 2020: Kanjwal et al., Journal of Innovations in Cardiac Rhythm Management (case report) documented new-onset postural orthostatic tachycardia syndrome (POTS) in an otherwise healthy female patient following COVID-19 infection

November 23, 2020: Kwon et al., Journal of Korean Medical Science (outbreak investigation) documented SARS-CoV-2 spread inside a restaurant where ceiling air conditioners directed airflow from an infected person to others up to 6.5 meters away after only minutes of exposure, showing that airflow can override distance and that spacing alone is not enough indoors.

November 25, 2020: Banerjee et al., Cell (lab study) showed that SARS-CoV-2 weakens the cell’s early immune defenses by blocking normal gene and protein production, helping the virus hide from interferons and spread more easily.

November 28, 2020: Vanaparthy et al., Cureus (case report) described a COVID-19 patient who developed unusual post-infection effects including vestibular neuritis (severe vertigo), facial nerve spasms, and Raynaud's phenomenon, highlighting that COVID-19 can trigger neurological and vascular symptoms beyond the lungs

December 3, 2020: Poston et al., Clinical Infectious Diseases (neutralization study) showed that antibodies from pre-pandemic seasonal coronavirus infections could neutralize common cold coronaviruses but did not neutralize SARS-CoV-2, arguing against widespread pre-existing antibody protection

December 3, 2020: Pellegrini et al., Cell (human brain organoid and cell culture study) showed that SARS-CoV-2 can target the brain’s choroid plexus, damaging a key protective barrier and triggering inflammation

December 7, 2020: Sterlin et al., Science Translational Medicine (longitudinal human immunology study) found that IgA dominates the early neutralizing antibody response to SARS-CoV-2, appearing before IgG, driving most early neutralization, and persisting longer at mucosal sites like saliva, highlighting the importance of mucosal immunity in early infection

December 7, 2020: Wang et al., Science Translational Medicine (human immunology/antibody engineering study) showed that dimeric IgA, the antibody form found in the nose and throat, neutralizes SARS-CoV-2 far more effectively than standard antibodies, explaining why early mucosal immunity plays such a critical role in blocking infection at the entry point

December 9, 2020: Moreno-Arrones et al., Journal of the European Academy of Dermatology and Venereology (prospective multicenter clinical) found that COVID-19 can trigger telogen effluvium, a temporary but intense hair-shedding condition, typically starting about 2 months after infection, even in some mild or asymptomatic cases

December 14, 2020: Harvey et al., Environmental Science & Technology Letters (longitudinal environmental surveillance) detected SARS-CoV-2 RNA on high-touch public surfaces but estimated the infection risk from touch as very low, reinforcing that fomites play a minimal role in transmission

December 15, 2020: Fabrizi et al., Pathogens (systematic review/meta-analysis) found that acute kidney injury (AKI) is common in COVID-19, affecting about 1 in 6 hospitalized patients, rising to around half of severe cases, and is strongly linked to higher mortality, establishing kidney injury as a major COVID complication