H5N1

The evolution of SARS-CoV-2 seroprevalence in Canada: A time-series study, 2020–2023

Via CMAJ: The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020–2023. The abstract:

Background: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity.  

Methods: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age.  

Results: By November 2021, 9.0% (95% credible interval [CrI] 7.3%–11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant — by Mar. 15, 2023, 76% (95% CrI 74%–79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia.  

Interpretation: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022

Via medRxiv: Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022. The underestimates of infections are breathtaking. The abstract:

Background  

We chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022.  

Methods  

Anonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections.  

Results  

Sero-prevalence was ≤1% by the 3rd snapshot in September 2020 and <5% by January 2021 (4th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), ∼80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained <15% through September/October 2021, increasing through subsequent Omicron waves to ∼40% by March 2022 (7th) and ∼60% by July/August 2022 (8th). By August 2022, at least 70-80% of children ≤19 years, 60-70% of adults 20-59 years, but ∼40% of adults ≥60 years had been infected. 

Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots. 

Interpretation  

By August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely dependent on vaccine-induced protection alone, and should be prioritized for additional doses. 

Competing Interest Statement  

DMS is Principal Investigator on grants from the Public Health Agency of Canada and Michael Smith Foundation for Health Research, paid to her institution, in support of this work and has received grants from the Canadian Institutes of Health Research and the BCCDC Foundation for Public Health, also paid to her institution, for other SARS-CoV-2 work. As the Provincial Health Officer with authority under the emergency provisions of the Public Health Act, BH authorized the access to and analysis of the anonymized sera used in this study; the study was separately reviewed and approved by the University of British Columbia Clinical Research Ethics Board. MK received grants/contracts paid to his institution from Roche, Hologic and Siemens. No other authors have conflicts of interest to disclose.

Molecular evidence for SARS-CoV-2 in samples collected from patients with morbilliform eruptions since late 2019 in Lombardy, northern Italy

Via ScienceDirect, a report in Environmental Research that could change the origin story of SARS-CoV-2: Molecular evidence for SARS-CoV-2 in samples collected from patients with morbilliform eruptions since late 2019 in Lombardy, northern Italy. The abstract:

As a reference laboratory for measles and rubella surveillance in Lombardy, we evaluated the association between SARS-CoV-2 infection and measles-like syndromes, providing preliminary evidence for undetected early circulation of SARS-CoV-2. 

Overall, 435 samples from 156 cases were investigated. RNA from oropharyngeal swabs (N = 148) and urine (N = 141) was screened with four hemi-nested PCRs and molecular evidence for SARS-CoV-2 infection was found in 13 subjects. Two of the positive patients were from the pandemic period (2/12, 16.7%, March 2020–March 2021) and 11 were from the pre-pandemic period (11/44, 25%, August 2019–February 2020). 

Sera (N = 146) were tested for anti-SARS-CoV-2 IgG, IgM, and IgA antibodies. Five of the RNA-positive individuals also had detectable anti-SARS-CoV-2 antibodies. No strong evidence of infection was found in samples collected between August 2018 and July 2019 from 100 patients. 

The earliest sample with evidence of SARS-CoV-2 RNA was from September 12, 2019, and the positive patient was also positive for anti-SARS-CoV-2 antibodies (IgG and IgM). Mutations typical of B.1 strains previously reported to have emerged in January 2020 (C3037T, C14408T, and A23403G), were identified in samples collected as early as October 2019 in Lombardy. One of these mutations (C14408T) was also identified among sequences downloaded from public databases that were obtained by others from samples collected in Brazil in November 2019. 

We conclude that a SARS-CoV-2 progenitor capable of producing a measles-like syndrome may have emerged in late June-late July 2019 and that viruses with mutations characterizing B.1 strain may have been spreading globally before the first Wuhan outbreak. Our findings should be complemented by high-throughput sequencing to obtain additional sequence information. 

We highlight the importance of retrospective surveillance studies in understanding the early dynamics of COVID-19 spread and we encourage other groups to perform retrospective investigations to seek confirmatory proofs of early SARS-CoV-2 circulation.

SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021

Via medRxiv: SARS-CoV-2 infection in Africa: A systematic review and meta-analysis of standardised seroprevalence studies, from January 2020 to December 2021. The abstract:

Introduction  

Estimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy.  

Methods  

We searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634.  

Results  

We identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence).  

Conclusion  

We report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.

See this Washington Post report for details of this and other studies indicating Africa has been hit far harder by COVID-19 than we imagined.

Two-thirds of Indians have coronavirus antibodies, survey shows

Via Reuters: Two-thirds of Indians have coronavirus antibodies, survey shows. That's about 1 billion people.

July 20 (Reuters) - Two-thirds of India's population have antibodies against the coronavirus, according to data released on Tuesday from a survey of 29,000 people across the nation conducted in June and July. 

The fourth national blood serum survey which tests for antibodies, known as a sero survey, included 8,691 children aged 6-17 years for the first time. Half of them were seropositive. 

The survey showed 67.6% of adults were seropositive, while more than 62% of adults were unvaccinated. As of July, just over 8% of eligible adult Indians had received two vaccine doses. 

About 400 million of India's 1.4 billion people did not have antibodies, the survey showed. 

India's daily cases have fallen to four-month lows after a second-wave that crippled the healthcare system. But experts have warned the authorities against swiftly reopening cities and voiced concerns about overcrowding at tourist sites. 

"The second wave is still persisting. The danger of new outbreaks is very much there," Vinod Kumar Paul, a top government adviser, told a news conference. 

"One out of three, wherever you are, ... is still vulnerable and therefore the pandemic is no way over," he said. 

The study also surveyed 7,252 healthcare workers and found 85% had antibodies, with one in 10 unvaccinated. 

Last month, data showed at least half of under-18s in India's financial capital of Mumbai were exposed to COVID-19 and had antibodies against it.

Some experts have said a third wave could hit children. Mumbai has joined other cities in building huge paediatric wards in preparation.

Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence

Via The Lancet, a very timely article: Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Excerpt:

After initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave. By contrast, in Manaus, Brazil, a study of blood donors indicated that 76% (95% CI 67–98) of the population had been infected with SARS-CoV-2 by October, 2020. High attack rates of SARS-CoV-2 were also estimated in population-based samples from other locations in the Amazon Basin—eg, Iquitos, Peru 70% (67–73). The estimated SARS-CoV-2 attack rate in Manaus would be above the theoretical herd immunity threshold (67%), given a basic case reproduction number (R0) of 3. 

In this context, the abrupt increase in the number of COVID-19 hospital admissions in Manaus during January, 2021 (3431 in Jan 1–19, 2021, vs 552 in Dec 1–19, 2020) is unexpected and of concern (figure). After a large epidemic that peaked in late April, 2020, COVID-19 hospitalisations in Manaus remained stable and fairly low for 7 months from May to November, despite the relaxation of COVID-19 control measures during that period.

There are at least four non-mutually exclusive possible explanations for the resurgence of COVID-19 in Manaus. First, the SARS-CoV-2 attack rate could have been overestimated during the first wave, and the population remained below the herd immunity threshold until the beginning of December, 2020. In this scenario, the resurgence could be explained by greater mixing of infected and susceptible individuals during December. The 76% estimate of past infection might have been biased upwards due to adjustments to the observed 52·5% (95% CI 47·6–57·5) seroprevalence in June, 2020, to account for antibody waning. 

However, even this lower bound should confer important population immunity to avoid a larger outbreak. Furthermore, comparisons of blood donors with census data showed no major difference in a range of demographic variables, and the mandatory exclusion of donors with symptoms of COVID-19 is expected to underestimate the true population exposure to the virus. Reanalysis and model comparison by independent groups will help inform the best-fitting models for antibody waning and the representativeness of blood donors. 

Second, immunity against infection might have already begun to wane by December, 2020, because of a general decrease in immune protection against SARS-CoV-2 after a first exposure. Waning of anti-nucleocapsid IgG antibody titres observed in blood donors might reflect a loss of immune protection, although immunity to SARS-CoV-2 depends on a combination of B-cell and T-cell responses. A study of UK health-care workers showed that reinfection with SARS-CoV-2 is uncommon up to 6 months after the primary infection. 

However, most of the SARS-CoV-2 infections in Manaus occurred 7–8 months before the resurgence in January, 2021; this is longer than the period covered by the UK study, but nonetheless suggests that waning immunity alone is unlikely to fully explain the recent resurgence. Moreover, population mobility in Manaus decreased from mid-November, 2020, with a sharp reduction in late December, 2020,suggesting that behavioural change does not account for the resurgence of hospitalisations. 

Third, SARS-CoV-2 lineages might evade immunity generated in response to previous infection. Three recently detected SARS-CoV-2 lineages (B.1.1.7, B.1.351, and P.1), are unusually divergent and each possesses a unique constellation of mutations of potential biological importance. Of these, two are circulating in Brazil (B.1.1.7 and P.1) and one (P.1) was detected in Manaus on Jan 12, 2021. One case of SARS-CoV-2 reinfection has been associated with the P.1 lineage in Manaus19 that accrued ten unique spike protein mutations, including E484K and N501K.16 Moreover, the newly classified P.2 lineage (sublineage of B.1.128 that independently accrued the spike E484K mutation) has now been detected in several locations in Brazil, including Manaus. P.2 variants with the E484K mutation have been detected in two people who have been reinfected with SARS-CoV-2 in Brazil, and there is in-vitro evidence that the presence of the E484K mutation reduces neutralisation by polyclonal antibodies in convalescent sera. 

Fourth, SARS-CoV-2 lineages circulating in the second wave might have higher inherent transmissibility than pre-existing lineages circulating in Manaus. The P.1 lineage was first discovered in Manaus.16 In a preliminary study, this lineage reached a high frequency (42%, 13 of 31) among genome samples obtained from COVID-19 cases in December, 2020, but was absent in 26 samples collected in Manaus between March and November, 2020. 

Thus far, little is known about the transmissibility of the P.1 lineage, but it shares several independently acquired mutations with the B.1.1.7 (N501Y) and the B.1.325 (K417N/T, E484K, N501Y) lineages circulating in the UK and South Africa, which seem to have increased transmissibility. Contact tracing and outbreak investigation data are needed to better understand relative transmissibility of this lineage.

SARS-CoV-2 antibody seroprevalence in India, August–September, 2020: Findings from the second nationwide household serosurvey

Via The Lancet Global Health: SARS-CoV-2 antibody seroprevalence in India, August–September, 2020: findings from the second nationwide household serosurvey. The summary:

Background 

The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May–June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0·73% (95% CI 0·34–1·13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. 

Methods 

We did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. 3–5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. 

Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys. 

Findings 

Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6·6% (95% CI 5·8–7·4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7·1% (6·2–8·2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. 

We estimated a cumulative 74·3 million infections in the country by Aug 18, 2020, with 26–32 infections for every reported COVID-19 case. 

Interpretation 

Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country.

Serologic testing of US blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020

Via Clinical Infectious Diseases: Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020. The abstract:

Background 

SARS-CoV-2, the virus that causes COVID-19 disease, was first identified in Wuhan, China in December 2019, with subsequent worldwide spread. The first U.S. cases were identified in January 2020. 

Methods 

To determine if SARS-CoV-2 reactive antibodies were present in sera prior to the first identified case in the U.S. on January 19, 2020, residual archived samples from 7,389 routine blood donations collected by the American Red Cross from December 13, 2019 to January 17, 2020, from donors resident in nine states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at CDC for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan Ig) enzyme linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor binding domain / Ace2 blocking activity assay.  

Results 

Of the 7,389 samples, 106 were reactive by pan Ig. Of these 106 specimens, 90 were available for further testing. Eighty four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor binding domain / Ace2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all nine states.  

Conclusions 

These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to January 19, 2020.

Estimated SARS-CoV-2 seroprevalence in the US as of September 2020

Via JAMA Network: Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020. The key points and abstract;

Key Points 

Question  What proportion of persons across 52 US jurisdictions had detectable antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from July to September 2020? 

Findings  In this repeated, cross-sectional study of 177 919 residual clinical specimens, the estimated percentage of persons in a jurisdiction with detectable SARS-CoV-2 antibodies ranged from fewer than 1% to 23%. Over 4 sampling periods in 42 of 49 jurisdictions with calculated estimates, fewer than 10% of people had detectable SARS-CoV-2 antibodies.  

Meaning  While SARS-CoV-2 antibody prevalence estimates varied widely across jurisdictions, most people in the US did not have evidence of previous SARS-CoV-2 infection.  

Abstract 

Importance  Case-based surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimates the true prevalence of infections. Large-scale seroprevalence surveys can better estimate infection across many geographic regions.  

Objective  To estimate the prevalence of persons with SARS-CoV-2 antibodies using residual sera from commercial laboratories across the US and assess changes over time. 

Design, Setting, and Participants  This repeated, cross-sectional study conducted across all 50 states, the District of Columbia, and Puerto Rico used a convenience sample of residual serum specimens provided by persons of all ages that were originally submitted for routine screening or clinical management from 2 private clinical commercial laboratories. Samples were obtained during 4 collection periods: July 27 to August 13, August 10 to August 27, August 24 to September 10, and September 7 to September 24, 2020. 

Exposures  Infection with SARS-CoV-2. 

Main Outcomes and Measures  The proportion of persons previously infected with SARS-CoV-2 as measured by the presence of antibodies to SARS-CoV-2 by 1 of 3 chemiluminescent immunoassays. Iterative poststratification was used to adjust seroprevalence estimates to the demographic profile and urbanicity of each jurisdiction. Seroprevalence was estimated by jurisdiction, sex, age group (0-17, 18-49, 50-64, and ≥65 years), and metropolitan/nonmetropolitan status.  

Results  Of 177 919 serum samples tested, 103 771 (58.3%) were from women, 26 716 (15.0%) from persons 17 years or younger, 47 513 (26.7%) from persons 65 years or older, and 26 290 (14.8%) from individuals living in nonmetropolitan areas. Jurisdiction-level seroprevalence over 4 collection periods ranged from less than 1% to 23%. In 42 of 49 jurisdictions with sufficient samples to estimate seroprevalence across all periods, fewer than 10% of people had detectable SARS-CoV-2 antibodies. Seroprevalence estimates varied between sexes, across age groups, and between metropolitan/nonmetropolitan areas. Changes from period 1 to 4 were less than 7 percentage points in all jurisdictions and varied across sites.  

Conclusions and Relevance  This cross-sectional study found that as of September 2020, most persons in the US did not have serologic evidence of previous SARS-CoV-2 infection, although prevalence varied widely by jurisdiction. Biweekly nationwide testing of commercial clinical laboratory sera can play an important role in helping track the spread of SARS-CoV-2 in the US.

What reinfections mean for COVID-19

Via The Lancet Infectious Diseases: What reinfections mean for COVID-19. Excerpt:

One of the key questions in predicting the course of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is how well and how long the immune responses protect the host from reinfection. For some viruses, the first infection can provide lifelong immunity; for seasonal coronaviruses, protective immunity is short-lived. 

In The Lancet Infectious Diseases, Richard L Tillett and colleagues describe the first confirmed case of SARS-CoV-2 reinfection in the USA. A 25-year-old man from the US state of Nevada, who had no known immune disorders, had PCR-confirmed SARS-CoV-2 infection in April, 2020 (cycle threshold [Ct] value 35·24; specimen A). He recovered in quarantine, testing negative by RT-PCR at two consecutive timepoints thereafter. 

However, 48 days after the initial test, the patient tested positive again by RT-PCR (Ct value 35·31; specimen B). Viral genome sequencing showed that both specimens A and B belonged to clade 20C, a predominant clade seen in northern Nevada. However, the genome sequences of isolates from the first infection (specimen A) and reinfection (specimen B) differed significantly, making the chance of the virus being from the same infection small. 

What is worrisome is that SARS-CoV-2 reinfection resulted in worse disease than did the first infection, requiring oxygen support and hospitalisation. The patient had positive antibodies after the reinfection, but whether he had pre-existing antibody after the first infection is unknown.  

This case report adds to rapidly growing evidence of COVID-19 reinfection, in which viral genomic sequences were used to confirm infections by distinct isolates of SARS-CoV-2. What do reinfection cases mean for public health and vaccination endeavors to stop the COVID-19 pandemic? 

Do reinfections occur because of a scant antibody response after first infection? Of the four reinfection cases reported to date, none of the individuals had known immune deficiencies. Currently, only two individuals had serological data from the first infection and one had pre-existing antibody (IgM) against SARS-CoV-2. Because of the wide range of serological testing platforms used across the globe, it is impossible to compare results from one assay to another. For example, antibody reactivity to nucleocapsid protein indicates previous exposure to SARS-CoV-2 but not whether antibodies that can block infection (anti-spike) are present. Also, antibody levels are highly dependent on the timing after exposure. The key goal for the future is to ascertain the level and specificity of antibody to spike protein at the time of reinfection, to determine immune correlate of protection. 

Does immunity protect an individual from disease on reinfection? The answer is not necessarily, because patients from Nevada and Ecuador had worse disease outcomes at reinfection than at first infection. It is important to keep in mind that the reinfection cases in general are being picked up because of symptoms and are biased towards detection of symptomatic cases. 

Due to the paucity of broad testing and surveillance, we do not know how frequently reinfection occurs among individuals who recovered from their first infection. Asymptomatic reinfection cases can only be picked up by routine community testing or at an airport, for example, and we are probably severely underestimating the number of asymptomatic reinfections. Why do some reinfections result in milder disease, whereas others are more severe? Further investigation is needed of pre-existing immune responses before second exposure, and viral inoculum load. 

Does infection by different viral isolates mean we need a vaccine for each type? While differences in the viral genome sequence of the various isolates are a great way to know if an individual is reinfected (ruling out reactivation of lingering virus infection), it does not indicate that the second infection was due to immune evasion. There is currently no evidence that a SARS-CoV-2 variant has emerged as a result of immune evasion. For now, one vaccine will be sufficient to confer protection against all circulating variants. Furthermore, reinfection by a distinct viral variant from the original virus does not imply immune escape.