Tag Archives: Coronavirus Disease COVID-19

Real-world data on the effectiveness of Sotrovimab as a prophylactic against COVID-19

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

In a recent study posted in the medRxiv* preprint server, scientists assessed the efficacy of sotrovimab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treatment.

Emerging SARS-CoV-2 variants have lowered the fold change in half maximal effective concentration (EC50) for the SARS-CoV-2 Omicron BA.2 sublineage and subsequent sublineages. Yet, the association between this decrease and clinical efficacy outcomes is unknown. With a lack of clinical trials evaluating the efficacy of sotrovimab against novel variants, real-world evidence becomes an essential data source.

Study: Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review. Image Credit: Cryptographer / ShutterstockStudy: Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review. Image Credit: Cryptographer / Shutterstock

About the study

In the present study, researchers assessed the efficacy of sotrovimab on severe coronavirus disease 2019 (COVID-19) outcomes throughout the period of the prevalence of the SARS-CoV-2 Omicron BA.2 subvariant.

This systematic literature review (SLR) comprised observational papers assessing clinical outcomes as well as the viral load in sotrovimab-treated patients, which were published between 1 January 2022 and 3 November 2022 in preprint articles, peer-reviewed journal publications, and conference abstracts. To identify data related to Omicron BA.2 and the following subvariants, the team chose a suitable publication period for the systematic review.

The following electronic databases were searched on 3 November 2022: MEDLINE, LitCovid, Embase, EcoLit, and Cochrane COVID-19 Study Registry. Further searches were undertaken in medRvix, bioRvix, arRvix, xhemRvix, Preprints.org, SSRN, and ResearchSquare for relevant preprints. In addition, relevant abstracts from the following conferences were indexed beginning in January 2022: Infectious Diseases Week, International Conference on Emerging Infectious Diseases, European Respiratory Society, and European Congress of Clinical Microbiology and Infectious Diseases.

Data extraction from the listed studies was conducted by a single extractor using a Microsoft Excel-designed data extraction file. Information extracted included the study’s title and citation, data source, study design and details, country, number of patients, study population, data collection period and circulating SARS-CoV-2 variants, duration of follow-up, key baseline features, and clinical outcomes. The clinical outcomes taken into account for the study included hospital admission, intensive care admission, respiratory support, emergency department visits, mortality, COVID-19 progression, the relative and absolute change in viral load observed during the acute phase after sotrovimab therapy, and the number of patients having undetectable viral load after sotrovimab treatment.

Results

Initial searches of electronic databases generated 257 studies. Another 263 studies were found by searching preprints, conference abstracts, and citation chasing from appropriate SLRs. After removing duplicates, 343 unique abstracts and titles were evaluated, of which 89 were deemed eligible for full-text review. Five observational trials reporting viral load or clinical outcome data associated with sotrovimab during the era of BA.2 predominance were deemed appropriate for inclusion in the present SLR.

Point estimates for hospitalization or mortality (as a composite endpoint) or clinical progression for sotrovimab-treated patients. a95 CIs calculated via Clopper-Pearson methods using reported data. bDefined as March through April 2022 in source and assumes homogeneity in the distribution of SARS-CoV-2 variants across all US states. cOnly COVID-19-specific outcome shown; all-cause outcome also reported in source. dHospitalizations were COVID-19-specific; deaths could be due to any cause. CI confidence interval

Point estimates for hospitalization or mortality (as a composite endpoint) or clinical progression for sotrovimab-treated patients. a95 CIs calculated via Clopper-Pearson methods using reported data. bDefined as March through April 2022 in source and assumes homogeneity in the distribution of SARS-CoV-2 variants across all US states. cOnly COVID-19-specific outcome shown; all-cause outcome also reported in source. dHospitalizations were COVID-19-specific; deaths could be due to any cause. CI confidence interval

The number of patients reporting hospitalization or fatality due to COVID-19 was consistently low for all investigations and periods of the prevalence of Omicron BA.1 and BA.2 variants. COVID-19-related hospital admission or mortality rates were between 1.0% and 3.1% for sotrovimab-treated patients during Omicron BA.1 prevalence and from 1.0% and 3.6% when BA.2 was predominant. The number of patients who reported hospitalization and mortality due to all causes ranged from 2.1% to 2.7% for the BA.1 predominance era, and from 1.7% to 2.0% for the BA.2 era. During Omicron BA.1 predominance, COVID-19-related mortality was projected to be 0.21% for the sotrovimab group versus 0.67% for the molnupiravir group, and 0.15% versus 0.96% for the BA.2 era, respectively.

During the BA.1 and BA.2 subvariant surges, sotrovimab was associated with a significantly decreased incidence of 28-day SARS-CoV-2-related hospital admission or fatality compared to molnupiravir. After statistical adjustment for demographics, vaccination status, high-risk cohort categories, body mass index, calendar time, and other comorbidities, the findings indicated that sotrovimab was associated with a significantly lower risk of COVID-19-related hospital admission or mortality compared to molnupiravir during the BA.1 and BA.2 periods.

During the BA.2 subvariant surge, sotrovimab was linked with a decreased risk of 30-day hospitalization or mortality from all causes compared to no mAb treatment. In March 2022, sotrovimab was considerably more successful than non-mAb-treated patients, with an adjusted reduction of 59% in relative risk and a propensity score-matched relative risk reduction of 64% with respect to 30-day all-cause hospital admission or mortality. Similar risks of hospitalization were associated with BA.1 and BA.2 patients treated with sotrovimab.

Conclusion

The study findings showed that sotrovimab continued to be clinically effective in mitigating severe clinical outcomes associated with SARS-CoV-2 infections during the period of SARS-CoV-2 Omicron BA.2 predominance compared to the control/comparator and relative to Omicron BA.1 predominance. During Omicron BA.1 and BA.2 subvariant predominance, the studies consistently reported low rates of poor clinical outcomes in individuals treated with sotrovimab.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Study finds community-onset bacterial coinfection in children with critical COVID-19 is infrequent but empiric antibiotics are commonly prescribed

In a recent study published in Open Forum Infectious Diseases, researchers evaluated the use of empiric antibiotics to determine the prevalence rates of community-acquired bacterial coinfections among hospitalized pediatric critical coronavirus disease 2019 (COVID-19) patients and to identify opportunities for de-escalating antibiotic usage in case of no bacteria-caused sepsis among high-risk individuals, and those presenting with shock.

Study: Community-onset bacterial coinfection in children critically ill with SARS-CoV-2 infection. Image Credit: nokwalai/Shutterstock
Study: Community-onset bacterial coinfection in children critically ill with SARS-CoV-2 infection. Image Credit: nokwalai/Shutterstock

Background

Community-acquired bacterial coinfections among hospitalized adult coronavirus disease 2019 (COVID-19) patients are uncommon; however, empiric antibiotic usage is reportedly high. Data on empiric antibiotic usage and bacterial coinfections among pediatric individuals with critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited.

The clinical manifestations of severe SARS-CoV-2 infections often include pulmonary distress and fever, findings that could be difficult to discriminate from serious bacterial infections, which might prompt the use of empiric antibiotics in the initial days of hospitalization, particularly among high-risk individuals.

About the study

In the present study, researchers investigated whether any radiographic, laboratory, or clinical features ascertainable during hospitalization were related to empiric antibiotic usage or were estimative of bacterial coinfections acquired in community settings.

The team evaluated individuals below 19.0 years and admitted to pediatric high-acuity units (HAU) or intensive care units (ICU) due to SARS-CoV-2 infections from March 2020 to December 2020. On the basis of microbiology reports from the initial 72 hours of hospitalization, the team adjudicated if patients had community-acquired bacterial coinfections.

Clinical and demographic variables of individuals with and without antibiotic prescriptions and bacterial coinfections in the initial days of hospitalization were compared. Poisson regression modeling was performed to assess factors related to the outcome, and the adjusted relative risk (aRR) values were calculated.

Data were obtained from patient electronic medical records and data from the nationwide overcoming COVID-19 population health active surveillance registry of patients hospitalized due to COVID-19-associated complications between 15 March 2020 and 31 December 2020 across >70.0 pediatric hospitals in 25 states.

COVID-19 diagnosis was confirmed using polymerase chain reaction (PCR). The team excluded multisystem inflammatory syndrome among children (MIS-C) patients diagnosed using the Centers for Disease Control and Prevention (CDC) criteria. Data were obtained on demographic parameters, clinical symptoms and signs, comorbidities, radiographical and laboratory investigations, and data on antibiotics prescribed at admission and the course of critical COVID-19, including clinical outcomes and hemodynamic and respiratory support needed.

The primary study outcome assessed was the prescriptions of empirical antimicrobials, for which enteral or intravenous antimicrobials administered in the initial two days of hospital admission were assessed. The second outcome evaluated community-acquired bacterial infection presence, for which relevant case report form (CRF) information from individuals with SARS-CoV-2-positive microbiological cultures, and PCR, were analyzed in the initial 72 hours of hospital admission.

Results

Out of 532 individuals, 63.0% were administered empiric antibiotics; however, only seven percent developed bacterial coinfections, of which only three percent were respiratory-type. Empirical antibiotics had a greater likelihood of being prescribed to immunosuppressed individuals (aRR of 1.3), requiring non-mechanical ventilator-type respiratory aid (aRR of 1.4), or requiring invasive-type mechanical ventilators (aRR of 1.8), than no respiratory aid.

The most frequently prescribed antimicrobials were ceftriaxone (41%) and vancomycin (28%), followed by cefepime (20%). Most individuals were prescribed multiple antimicrobials, with 21%, 10%, and 18% receiving 2.0, 3.0, and ≥4.0 antibiotics in the initial two days of hospital admission. More than 33% of individuals received antibiotics for ≥5.0 days, despite no evidence of bacterial coinfections. The median social vulnerability index (SVI) values were significantly greater among those who received antibiotics than those who did not.

The median C-reactive protein (CRP) levels were greater among those who received antibiotics versus those who did not (4.6 mg per dL vs. 2.2 mg per dL), as were the median procalcitonin levels (0.4 ng per mL vs. 0.1 ng per mL). The median leukocyte counts showed no significant differences between the two groups. Antibiotic usage was related to COVID-19 severity, indicated by greater median values for PEdiatric Logistic Organ Dysfunction-2 (PELOD-2) scores at hospitalization among individuals who received antibiotics than those who did not.

Seven percent (n=38) of individuals had true community-onset bacterial coinfections, of which 13, 16, 8.0, and 4.0 were bloodstream infections, respiratory infections, urinary tract infections, and bacterial infections at other sites (peritonitis, colitis, meningitis, and pharyngitis), respectively.

No particular pathogenic organism predominantly caused bacterial coinfections, although most pulmonary coinfections were caused by Staphylococcus aureus and/or Pseudomonas aeruginosa. Greater PELOD-2 scores at admission were associated with bacterial coinfections (aRR of 1.2), in addition to age, sex, and pulmonary conditions other than asthma (aRR 2.3).

Conclusion

Overall, the study findings showed that community-onset bacterial coinfections among children with critical COVID-19 are not frequent; however, empiric antibiotics are usually prescribed. The study findings inform antibiotic use and underpin swift de-escalation in case assessments indicating that coinfections are not likely.

Journal reference:

Maternal and perinatal outcomes of women infected with SARS-CoV-2 during the Omicron wave in Italy

In a recent study published in the Clinical Microbiology and Infection, researchers assessed the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on pregnant women during the Omicron wave.

Study: Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system. Image Credit: GolF2532/Shutterstock
Study: Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system. Image Credit: GolF2532/Shutterstock

Background

During the coronavirus disease 2019 (COVID-19) pandemic, pregnant women were more likely than the general population to develop severe COVID-19. In utero mother-to-child viral transmission was shown to be uncommon, and infected mothers demonstrated a strong immune response with anti-SARS-CoV-2 antibodies passed on to newborns.

Despite many studies indicating a substantial maternal antibody response to SARS-CoV-2 immunization and the absence of safety issues, the vaccination rate among pregnant women remained lower than that of the general population. Only a few studies have been undertaken to date on the impact of the SARS-CoV-2 Omicron variant on unvaccinated and vaccinated pregnant women.

About the study

In the present study, researchers compared the perinatal and maternal outcomes of SARS-CoV-2-infected women in Italy during the SARS-CoV-2 Omicron variant wave based on their vaccination protection.

The current national prospective cohort research involved pregnant women who tested COVID-19-positive within seven days of hospitalization in any Italian maternity unit between January 1 and May 31 2022. In addition, women reported whether they had received the SARS-CoV-2 vaccine, as well as the when (before and/or at the time of pregnancy) and how many doses were received.

The primary outcome measure was SARS-CoV-2 disease severity, classified as mild, moderate, or severe. The two most severe severity categories, determined by pneumonia diagnosis, were grouped together for statistical analysis as “moderate or severe COVID-19 disease” (MSCD). Secondary outcomes comprised preterm birth, stillbirth, delivery mode, admission to the neonatal intensive care unit (NICU), and early neonatal mortality before hospital release.

MSCD protection was taken into account as an exposure variable. Women vaccinated with a minimum of one vaccine dose at the time of pregnancy, and those vaccinated with the full vaccine schedule and the first booster vaccine were protected against MSCD. On the other hand, unvaccinated women and participants who were vaccinated with either one or two vaccine doses prior to pregnancy and tested positive for SARS-CoV-2 at 22 or more gestational weeks were deemed unprotected. Women with incomplete vaccination information and those who were vaccinated with one or two doses prior to pregnancy and who tested positive for SARS-CoV-2 at less than 22 gestational weeks were deemed “unknown in terms of protective status.”

Results

Between January 1 and May 31, 2022, a total of 2,774 women who tested positive for SARS-CoV-2 within seven days of hospitalization were enrolled. Information was available about the protection status of 2147 women, while no significant clinical or socio-demographic variations were noted between these women and the entire cohort.

According to the study’s definition, almost 1,069 (49.8%) individuals were protected against MSCD. Of them, 74 were vaccinated with one vaccine during pregnancy, while 596 received two, including a minimum of one dose administered during pregnancy, while 327 received their first booster. In contrast, 1,078 women were deemed unprotected, including 989 women who were unvaccinated and 89 who tested positive for SARS-CoV-2 at 22 or more weeks of gestation after receiving one or two doses before pregnancy. All except 26 women were immunized with the conventional vaccinations alone or in conjunction with messenger ribonucleic acid (mRNA) vaccines.

Compared to protected women, unprotected women displayed a higher likelihood of being younger, less educated, of foreign nationality, and symptomatic. Also, 96.4% were hospitalized for childbirth or obstetrical causes, whereas 3.6% were hospitalized due to COVID-19. Eight of the latter acquired severe disease, 12 developed a moderate disease, and 58 developed a mild disease.

MSCD illness was uncommon overall but more prevalent among unprotected women than among protected women. Among the 41 MSCD cases, 27 of 29 unprotected women had not received any vaccine, while two were vaccinated with two doses prior to pregnancy. Three of the 12 protected women received the booster, while nine received two doses, among which the first was received before and the second was received during pregnancy.

Among unprotected women, seven out of eight severe infection cases and one maternal fatality occurred. COVID-19 pneumonia was deemed the cause of death, reported two weeks after delivery. Unprotected women had a greater incidence of MSCD compared to protected women, Asian women, and those with a history of comorbidities.

Sensitivity analysis revealed that unprotected women had considerably higher MSCD risk than protected women. Furthermore, 8.7% of newborns were born preterm, predominantly late preterm, with no significant variations between unprotected and protected women, but C-section was reported in 34.4% and 29.3% of women, respectively. The rate of preterm birth was greater among MSCD-infected women compared to those with milder cases and those with CS. Also, out of 619 CS cases, five were urgent/emergent due to COVID-19, and all involved MSCD-affected women.

Conclusion

Overall, the study findings documented a low prevalence of severe SARS-CoV-2 infection in pregnant women and considerable efficacy of the COVID-19 vaccine in providing protection. These statistics can serve as the foundation for informing pregnant women uncertain about the vaccine’s efficacy and demonstrating the importance of vaccination in protecting their newborns.

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Study compares effectiveness of Pfizer vs. Moderna booster COVID vaccines after third dose

In a recent scientific paper published in the journal Nature Microbiology, researchers reproduced two target trials using electronic health records (EHRs) of the Department of Veterans Affairs (VA) to compare the effectiveness of the third dose of BNT162b2 or messenger ribonucleic acid (mRNA)-1273 vaccine among United States (US) veterans.

Study: Comparative effectiveness of third doses of mRNA-based COVID-19 vaccines in US veterans. Image Credit: Steve Heap / ShutterstockStudy: Comparative effectiveness of third doses of mRNA-based COVID-19 vaccines in US veterans. Image Credit: Steve Heap / Shutterstock

Background

There is a lack of head-to-head comparative studies of the effectiveness of a third booster dose of different mRNA-technology-based coronavirus disease 2019 (COVID-19) vaccines. An ideal comparative effectiveness study of mRNA vaccines should cover racially diverse populations and evaluate possible differences in vaccine efficacy based on the time when an individual completed the primary vaccination series. Most importantly, these studies should account for the time windows of the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

During the current SARS-CoV-2-induced pandemic, vaccination effectively reduced the burden of severe disease and death from COVID-19. Especially, booster doses of BNT162b2 and mRNA-1273 vaccines countered waning immunity and broadened protection against novel, highly transmissible SARS-CoV-2 variants. In one of their previous work covering 439,684 US veterans, researchers found that both mRNA-1273 and BNT162b2 lowered the risk of SARS-CoV-2 infection and severe disease outcomes during SARS-CoV-2 Alpha variant prevalence.

About the study

In the present study, researchers matched recipients of  BNT162b2 or mRNA-1273 vaccines in a 1:1 ratio based on their risk factors to estimate their comparative effectiveness over 16 and nine weeks in the Delta-Omicron and Omicron period, respectively, for five COVID-19 outcomes:

  • reported SARS-CoV-2 infection,
  • reported symptomatic SARS-CoV-2 infection,
  • SARS-CoV-2 infection-related hospitalization,
  • intensive care unit (ICU) admission, and
  • death.

The veterans in the first emulated trial received the third dose of BNT162b2 or mRNA-1273 vaccines between 20 October 2021 and 8 February 2022. This period corresponded to SARS-CoV-2 Delta and Omicron variants prevalence. For each veteran in the primary analysis, the team started follow-up on the day of the third vaccination (baseline). It ended 16 weeks after baseline, death, or the end of study duration, i.e., 15 February 2022, as applicable.

The veteran population of the second emulated trial received the third dose of any of the two mRNA COVID-19 vaccines between 1 January and 1 March 2022, the period of only Omicron predominance. The median follow-up continued over nine weeks, during which the team documented 214 SARS-CoV-2 infections.

Study findings

In the first emulated trial, 147,553 and 214,728 veterans received the third dose of BNT162b2 and mRNA-1273, respectively. The baseline characteristics of 65,196 BNT162b2 recipients matched to an equal number of mRNA-1273 recipients were comparable compared to the eligible population. The median age of this veteran population was 70 years, 96% were males, and 24% were Blacks.

During the 16-week follow-up spanning Delta and Omicron prevalence, the researchers documented 2,994 SARS-CoV-2 infections, of which 200 were symptomatic COVID-19 cases, 194 sought hospitalization, 52 needed ICU admission, and 22 culminated in death. During this time, the estimated risk of reported infection for the BNT162b2 and mRNA-1273 third dose was 353.9 and 308.5 events per 10,000 individuals, respectively.

In the second emulated trial, 25,557 and 36,809 eligible veterans received the third dose of BNT162b2 mRNA-1273, respectively. Like in the first trial, the matched population comprised 7,894 BNT162b2 and an equal number of mRNA-1273 recipients with comparable baseline demographic and clinical characteristics relative to the eligible population. They had a higher proportion of men and White people.

During nine weeks of follow-up amid Omicron predominance, the estimated risk of documented SARS-CoV-2 infection was higher with a third dose of the BNT162b2 vaccine vs. mRNA-1273. Accordingly, the estimated risk ratio was 1.57, presented as events per 10,000 individuals.

Conclusions

The present study remarkably showed the comparative effect of the third (booster) dose of two mRNA vaccines, BNT162b2  and mRNA-1272, among a nationwide cohort of US veterans. Both vaccines reduced the absolute risks of breakthrough SARS-CoV-2 infections and severe COVID-19 outcomes. However, mRNA-1273 recipients had a lower risk of COVID-19-related adverse events over 16 weeks of follow-up than the mRNA-1273 vaccine recipients, particularly for reported SARS-CoV-2 infections. The findings remained comparable across periods spanning Delta and Omicron predominance and only Omicron predominance. The authors advocated continuous evaluation of the comparative effectiveness and safety of additional (booster) doses of COVID-19 mRNA vaccines in the future.

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Exploring dynamics of emergence and spread of SARS-CoV-2 variants of concern

In a recent study posted to the medRxiv* preprint server, researchers evaluated the emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in Canada.

Study: Emergence and Spread of SARS-CoV-2 Variants of Concern in Canada: a Retrospective Analysis from Clinical and Wastewater Data. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock
Study: Emergence and Spread of SARS-CoV-2 Variants of Concern in Canada: a Retrospective Analysis from Clinical and Wastewater Data. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock

Wastewater-based epidemiology (WBE) can ascertain the proportion of viral RNA by applying polymerase chain reaction (PCR) or sequencing techniques. WBE helps inform the public and health officials about coronavirus disease 2019 (COVID-19) outbreaks and trends. As such, clinical and wastewater surveillance data can be leveraged to improve estimates of VOC prevalence.

About the study

In the present study, researchers retrospectively analyzed the dynamics of SARS-CoV-2 VOC emergence and spread using clinical and wastewater data in Canada. The Public Health Agency of Canada (PHAC) records clinical COVID-19 case data. Some entries have data on the infecting SARS-CoV-2 variant/lineage determined by genome sequencing or screening via a discriminatory assay.

The PHAC, Statistics Canada, and the National Microbiology Laboratory (NML) initiated a pilot program in October 2020 to test for SARS-CoV-2 in wastewater specimens collected twice/thrice a week 15 from sewage treatment plants in multiple cities, including Edmonton, Montreal, Vancouver, Halifax, and Toronto. Besides, wastewater sampling was performed five times a week from three plants in Winnipeg.

Samples from these cities were shipped to NML for quantitative PCR (qPCR) analysis. In addition, the researchers included qPCR data on wastewater sampled three times a week from Saskatoon by the University of Saskatchewan. The NML and the University of Saskatchewan quantified the proportion of VOCs in wastewater. The authors focused on four SARS-CoV-2 VOCs (Alpha, Gamma, Delta, and Omicron) in this study.

Using PHAC records, VOC-infected clinical cases were identified, and confidence intervals (CIs) for the proportions of each variant were computed. To compute the growth rate, the authors assumed that time-dependent proportions of SARS-CoV-2 VOCs followed a logistic growth model during each wave. A similar logistic growth model with a hierarchical structure was applied to aggregate province-level clinical surveillance data into national estimates.

VOC proportions measured in wastewater were the percentages of variant alleles detected by assays. Due to limited data, wastewater data were not used to derive CIs or fit logistic models. Therefore, the growth rate of each variant was assessed using clinical data alone. Nonetheless, VOC proportions in wastewater were compared to those from clinical surveillance to assess similarities.

Findings

Results from the following provinces with large sample sizes were reported – Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Ontario, Quebec, and Saskatchewan. The authors observed similar trends in SARS-CoV-2 VOC proportions across all provinces in clinical and wastewater data. In the Summer of 2021, Alpha, Gamma, and Delta VOCs likely cocirculated in Alberta, Saskatchewan, and British Columbia.

SARS-CoV-2 VOC transitions appeared faster in Quebec and Ontario. The proportion of unidentified VOCs in clinical data in each province was less than 80%, except during the early Alpha wave and post-July 2021 in Manitoba and Quebec. The proportions of SARS-CoV-2 VOCs in wastewater exhibited trends similar to those measured by clinical surveillance, particularly for the Omicron variant.

The Gamma VOC significantly circulated only in British Columbia, whereas the other three VOCs of interest circulated in all provinces. The Delta VOC spread at similar speeds across provinces, with Newfoundland and Labrador being the only outlier, likely due to the small sample size. Likewise, the Omicron VOC spread at a similar rate in provinces. SARS-CoV-2 Delta became predominant within four months.

Contrastingly, the Omicron VOC was the major circulating variant within a month. Posterior estimates suggested that the Alpha, Delta, and Omicron VOCs were spread throughout Canada by early January 2021, July 2021, and January 2022, respectively. In contrast, the maximum national proportion of the Gamma variant, which failed to spread throughout Canada, was approximately 25%.

Conclusions

To summarize, the study reported the spread of SARS-CoV-2 Alpha, Gamma, Delta, and Omicron VOCs in seven provinces in Canada using wastewater and clinical surveillance data. The researchers observed synchrony in SARS-CoV-2 VOC introduction across jurisdictions with similar speeds for each variant. This was remarkable, given the differences between provinces in implementing public health measures for COVID-19 management.

SARS-CoV-2 Gamma and Delta, which harbor few mutations, required four months to become the dominant variant. By contrast, the Omicron variant, which carries several novel mutations, became predominant in less than a month. Overall, WBE can complement clinical surveillance and serve as a viable indicator of SARS-CoV-2 VOC circulation in communities.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Researchers explore the correlation between the dynamic shedding pattern of SARS-CoV-2 and viral load

In a recent article published in Nature Reviews Microbiology, researchers attempted to establish an association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, indicating its ribonucleic acid (RNA) levels, and the presence of infectious virions.

Study: SARS-CoV-2 viral load and shedding kinetics. Image Credit: CROCOTHERY/Shutterstock
Study: SARS-CoV-2 viral load and shedding kinetics. Image Credit: CROCOTHERY/Shutterstock

Additionally, they examined host and other biological factors that affect infectious virion(s) shedding by SARS-CoV-2. They also evaluated the strengths and limitations of diagnostic tools that might help precisely estimate viral load, a robust substitute for characterizing the shedding of infectious virions by SARS-CoV-2.

Background

SARS-CoV-2 shedding patterns have become unique and distinguished from that of its ancestral strain in three years of the coronavirus disease 2019 (COVID-19) pandemic. The emergence of SARS-CoV-2 variants of concern (VOCs) has likely further complicated this pattern.

A detailed understanding of viral shedding patterns is crucial for designing public health interventions to contain human-to-human SARS-CoV-2 transmission. Although multifactorial, biological characteristics of SARS-CoV-2 and its variants, host factors, and pre-existing immunity of the diseased individual affect the shedding of its infectious virions, which, in turn, determines its onward transmission.

Nevertheless, viral load is a key parameter for estimating SARS-CoV-2 infectiousness, and a higher viral load in an infected individual’s upper respiratory tract (URT) implies a greater risk for onward transmission. To date, no diagnostic test precisely identifies or distinguishes between replication-competent SARS-CoV-2 and its residual RNA.

Factors at play in SARS-CoV-2 viral load and infectious virion(s) shedding dynamics

Reverse transcription-polymerase chain reaction (RT-PCR) assay, for instance, only detects viral RNA with high sensitivity in the respiratory tract of an infected individual, which remains detectable even in the absence of infectious virions. It presents results as viral RNA copies per milliliter of swab sample or by the discretionary test-specific cycle threshold (CT) value. Then, there could be SARS-CoV-2 RNA in peripheral blood, urine, ocular secretions, and the patient’s stool. Yet again, diagnostic tests are unable to detect infectious viruses in these non-respiratory specimens.

Contrastingly, RT-PCR estimates infectiousness qualitatively or quantitatively by viral replication in cell culture. Clinical samples with lower viral load often show delayed development of a cytopathic effect (CPE). Likewise, there are other methods for infectious virion quantification, such as plaque assays and focus-forming assays, to name a few. If swab samples are not immediately submerged in a viral transport medium and stored at −80 °C after collection, it loses viability resulting in complete loss of infectious virions. Other factors influencing successful virus isolation include cell lines used for isolation. Most importantly, working with SARS-CoV-2 infectious virions requires adherence to biosafety level 3 conditions, and detection of the viable virus is restricted to research only, deemed unsuitable for diagnostics. Likewise, CT values are only a weak predictor of infectious virions in the first five days post-onset of symptoms (dpos).

Antigen-detecting (rapid) diagnostic tests (Ag-RDT) fetch faster results and are inexpensive. They show good harmony with RT-PCR positivity when CT values are below 25 to 30, a viral load suggesting the presence of infectious virions; however, they fetch unreliable results at higher CT values. Further, it remains unclear whether Ag-RDT positivity beyond 10 dpos correlates with infectious virion(s) shedding. With the increasing presence of mucosal antibodies and rising hybrid immunity, Ag-RDTs may further lose sensitivity.

It is worth noting that it is difficult to estimate the time for which a SARS-CoV-2-infected individual remains infectious. A patient’s age, gender, immunity, and infecting variant; all these factors and more influence viral shedding dynamics. Studies showing the difference in the infectious virus titers between Alpha and Delta VOCs and ancestral SARS-CoV-2 have consistently fetched conflicting results. Nevertheless, both VOCs generate higher viral RNA loads than the parental strain, with an increased probability of cell culture isolation.

Despite its high transmissibility, Omicron led to much lower RNA viral loads and cell culture isolation probability. Studies have observed different behaviors of Omicron sublineages concerning infectious virus titers, with Omicron BA.2 leading to higher RNA viral loads and taking more time to clear infection than Omicron BA.1.

Infectious virion shedding by the ancestral SARS-CoV-2 strain resolved faster in those under 18 year-olds compared to individuals >50 years of age. A study showed its higher RNA loads for prolonged times in men infected with Alpha or Delta VOCs than in women. Furthermore, population-scale analysis of viral RNA loads in different age groups showed minimal differences in the dissemination of SARS-CoV-2 RNA load between adults and children; however, it had diminished in those below five years.

Studies have estimated the average incubation period of ancestral SARS-CoV-2 between 4.6 and 6.4 days. However, as the time of infection is often unknown, researchers use dpos when analyzing viral load and infectious virions. However, findings concerning viral shedding patterns have shown considerable heterogeneity in symptomatic and asymptomatic COVID-19 patients. Regardless of clinical symptoms, studies have detected high viral loads in the URT of infected individuals, which makes clinical symptoms – a not-so-robust indicator of infectiousness.

Likewise, the viral load of an index case is an unreliable proxy for SARS-CoV-2 transmission. Viral load can substantially vary between two individuals due to susceptibility and immunity from previous infections or vaccination, which affects their disposition to transmit SARS-CoV-2. In the same way, some sites, in particular, represent a higher risk of transmission; accordingly, many SARS-CoV-2 superspreading events typically occurred indoors in crowded places, such as music auditoriums, cruise ships, care centers, and hospitals.

Researchers have been pursuing several approaches to find a proxy for infectiousness to guide SARS-CoV-2 isolation techniques. In this context, single guide RNAs, transcribed in SARS-CoV-2-infected cells but not packaged in their infectious virions, could serve as a good proxy of infectious virions. However, the assays devised to detect sgRNAs with specific RT-PCR assays have yet to be successfully incorporated into routine diagnostic tools owing to their lower sensitivity. Also, the absence of sgRNA does not necessarily indicate infectiousness but the absence of active SARS-CoV-2 replication.

Conclusions

To summarize, all the currently available diagnostic tools have limitations concerning infectious SARS-CoV-2 virion detection. Though they have not been able to contain every SARS-CoV-2 infection, they are indispensable components of the anti-COVID-19 public health arsenal that have helped reduce the number of infectious individuals in the community and, subsequently, the number of secondary transmissions. Concerted and continuous efforts to evaluate viral-shedding characteristics amid changing biological properties of emerging SARS-CoV-2 variants would remain highly significant and help inform global future public health policies.

Journal reference:

Do previously infected individuals still benefit from vaccination against COVID-19?

In a recent study published in PLOS Medicine, researchers determined the vaccine effectiveness (VE) of the primary coronavirus disease 2019 (COVID-19) vaccination series. They determined VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection, COVID-19-related hospitalization, and mortality. In this way, the researchers assessed the effect of time since vaccination during the predominance eras of different SARS-CoV-2 variants, viz., Alpha, Delta, and Omicron.

Study: Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha, Delta, or Omicron dominance: A Danish nationwide study. Image Credit: LookerStudio/Shutterstock
Study: Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha, Delta, or Omicron dominance: A Danish nationwide study. Image Credit: LookerStudio/Shutterstock

Background

In Denmark, the government provides free COVID-19 testing, vaccines, and medical care to all its residents. They rolled out the COVID-19 vaccination program in December 2020, prioritizing the elderly and people at high risk of severe disease. Likewise, they started a booster vaccination program in September 2021.

Scientific data points to the reduced effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant. Studies have also shown that natural immunity more effectively protects against SARS-CoV-2 reinfections than vaccination. Thus, it is in the public health interest to examine the additional benefits of vaccination (if any) among individuals previously infected with SARS-CoV-2.

About the study

In the present study, researchers compiled data from four nationwide resources, the Danish Civil Registration System (CRS), Danish Microbiology Database (MiBa), Danish Vaccination Registry (DVR), and Danish National Patient Registry (DNPR).

Combined with a unique personal registration number of a Danish citizen, this data helped them identify people with a confirmed SARS-CoV-2 infection between 1 January 2020 and 31 January 2022. Likewise, they obtained each SARS-CoV-2 variant’s dominance periods using CSR data, defined as the period when a variant accounted for 75% or more of all whole genome sequenced reverse transcription-polymerase chain reaction (RT-PCR) tests. Additionally, the team investigated COVID-19-related hospitalization up to 14 days after or 48 hours before SARS-CoV-2 reinfection and death within 30 days of reinfection.

In statistical analyses, they included gender, comorbidity, and country of origin as categorical variables, while age and hospital stay duration as time-varying covariates. The team used a quasi-Poisson regression model to estimate crude incidence rate ratios (IRRs) and a Cox proportional hazards regression model to estimate hazard ratios (HRs) adjusted for all variables before and in the respective periods after vaccination. Finally, they calculated VE crude (VEcrude) and adjusted (VEadjusted) as a percentage using IRR and HR values.

Study findings

The study population comprised 209,814, 292,978, and 245,530 individuals infected before or during the Alpha, Delta, and Omicron predominance eras, respectively. Of these, 19.2%, 64.9%, and 64.6% of people had received their COVID-19 primary vaccination during the Alpha, Delta, and Omicron periods, respectively. The primary study finding was that previously infected individuals also benefited from COVID-19 vaccination during all three variant periods, data crucial to inform policymakers plan future vaccination strategies.

In the Alpha-dominated period, the VE was not statistically significant. It peaked at 71% at 104 days or more after vaccination with any COVID-19 vaccine type. However, the VE against reinfection was highest between 14 and 43 days after the primary vaccination series in the Delta (94%) and Omicron (60%) periods. Though lower than for other variants, the researchers noted an initial VE of 60% against reinfections even during the Omicron period. These results are consistent with findings of a Qatar study showing a VE of 55.1% against reinfection with Omicron after two doses of a COVID-19 mRNA vaccine.

Since older and more vulnerable people received SARS-CoV-2 vaccination on priority. These individuals mounted a slower immune response following vaccination, explaining why the observed VE was statistically insignificant during the Alpha period. Moreover, all 65 years or older individuals experienced more severe outcomes than SARS-CoV-2 reinfections in other age groups, overall and within the same variant period.

Another intriguing finding was that the risk of COVID-19-related hospital admission during the Alpha period was higher for vaccinated vs. unvaccinated individuals (IR: 0.002 vs. 0.001). Perhaps even before the rollout of vaccines, several long-term care facilities (LTCF) residents had already contracted SARS-CoV-2 infections. Because the hospitalization and death events due to COVID-19-induced complications were too few in the present study, the researchers could not estimate VE for the same.

The completeness of the Danish registry data likely removed all unmeasured biases that might have impacted the study results. However, studies with longer follow-up times could ascertain VE against severe COVID-19 outcomes in those with prior infection.

Journal reference:

SARS-CoV-2 detected in white-tailed deer in Canada

In a recent study published in Nature Microbiology, researchers investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in white-tailed deer.

Study: Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission. Image Credit: Holly Kuchera/Shutterstock
Study: Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission. Image Credit: Holly Kuchera/Shutterstock

Background

Wildlife reservoirs of viruses with a broad host range can facilitate the emergence of human-infecting viral variants. There is phylogenomic evidence of the continuous transmission of SARS-CoV-2 from humans to Odocoileus virginianus or white-tailed deer in North America. However, there is no evidence of viral transmission from deer to humans.

About the study

In the present study, researchers determined the extent of SARS-CoV-2 infection in white-tailed deer and the chances of deer-to-human transmission of the virus.

During the yearly shooting season between 1 November and 31 December 2021, the team sampled 300 white-tailed deer in Eastern and Southwestern Ontario, Canada. Most white-tailed deer in the sample were adults, with equal proportions of males and females. Approximately 213 nose swabs and tissue samples were obtained from 294 retropharyngeal lymph nodes (RPLN). These were analyzed by reverse transcription polymerase chain reaction (RT–PCR) for SARS-CoV-2 ribonucleic acid (RNA).

Three high-quality SARS-CoV-2 consensus genomes were sequenced from five SARS-CoV-2 positive nasal swabs with a standard amplicon-based technique employed to estimate the viral lineage and perhaps deduce significant epidemiological relationships. For confirmation, each sample was extracted and sequenced individually using a capture-probe-based method.

The prevalence of mutations was evaluated in the Global Initiative on Sharing All Influenza Data (GISAID) and within animal-derived variants of concern (VOC) to recognize and contextualize essential mutations. This was achieved using five complete deer-derived sequences along with human-derived sequences.  Viral isolation was performed on Vero E6 cells that expressed human transmembrane protease serine 2 (TMPRSS2) to test the infectivity of the SARS-CoV-2 positive samples.

Results

Out of the 213 nose swabs collected, five tested positive based on the results of two independent RT-PCR analyses conducted at separate institutions. Additionally, 16 RPLNs were validated by PCR. SARS-CoV-2 RNA was found in 21 samples, which accounted for 6% of white-tailed deer harvested by hunters. All SARS-CoV-2 positive animals were adult white-tailed deer found in Southwestern Ontario, with the majority female.

Combining the sequence data obtained from the amplicon and capture-probe led to the recovery of five high-quality genomes with two incomplete genomes. Most of the non-SARS-CoV-2 reads matched that of the reference genome of the white-tailed deer, indicating that contamination with human-derived SARS-CoV-2 sequences was extremely unlikely. The team also noted that the viral genomes derived from the deer samples created a highly divergent clade in the B.1 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineage/20C Nextstrain clade, which had a most recent common ancestor (MRCA).

The Ontario deer lineage constitutes a very lengthy branch having 76 conserved nucleotide mutations compared to those in the SARS-CoV-2 Wuhan Hu-1 strain and 49 as compared to their most recent common ancestor with other GISAID genomes. Human-derived sequences obtained from Michigan, US, were estimated to share an MRCA between May and August 2020 with the Ontario deer lineage. These sequences obtained from humans are closely connected to a mixed clade of mink and human sequences collected in September and October 2020 in Michigan. The white-tailed deer lineage in Ontario has been identified as PANGO lineage B.1.641.

Among the 76 mutations that were similar among the six B.1.641 sequences, nine were in the SARS-CoV-2 spike (S), while 51 were in the open-reading frame (ORF)-1ab. The six nonsynonymous mutations in S include five substitutions and a six-nucleotide deletion. These S mutations, except H49Y, evolved before the divergence of B.1.641 lineage from the MRCA shared by the Michigan samples. Furthermore, only a few S mutations were preserved throughout B.1.641, S:L1265I, and S:613H and were unique to the human sample. Three other nonsynonymous mutations were detected in either 4658 or 4662 white-tailed deer samples, while 4662S:L959 exhibited a frameshift.

The team observed that four days post-infection, four of the samples displayed that 50% or less of the cell monolayer was affected by the cytopathic effect. In comparison to the original swab consensus sequences, confirmatory sequencing revealed only small frequency variations corresponding to one or two single-nucleotide polymorphism (SNP) changes.

Unlike SARS-CoV-2 Omicron, which needed three vaccine doses to neutralize B.1.641S, sera from vaccinated patients who had received two or three doses and sera from convalescent persons effectively neutralized all B.1.641S proteins. Importantly, there was no change in the neutralizing ability of sera against SARS-CoV-2 D614G or other SARS-CoV-2 isolates from Ontario white-tailed deer. Collectively, these findings imply that mutations in the S-gene of the white-tailed deer do not have a significant antigenic effect on antigenicity.

Conclusion

Overall, the study findings highlighted a distinct SARS-CoV-2 lineage in white-tailed deer and provided evidence of host adaptability and transient transfer from deer to humans. White-tailed deer have numerous characteristics essential for a viral reservoir to be sustained, including social behavior, highly transitory populations with multiple human–deer encounters, high density, and sylvatic relationships with other animals.

Journal reference:

Long COVID, a new clinical entity constantly evolving

A recent Journal of Microbiology, Immunology, and Infection study discusses the epidemiology, diagnosis, pathogenesis, and treatment of long coronavirus disease 2019 (COVID-19).

Study: Long COVID: An inevitable sequela of SARS-CoV-2 infection. Image Credit: fizkes / Shutterstock.com

Study: Long COVID: An inevitable sequela of SARS-CoV-2 infection. Image Credit: fizkes / Shutterstock.com

What is long COVID?

COVID-19 manifests as mild or asymptomatic illness in most patients; however, some patients develop severe disease or acute respiratory distress syndrome (ARDS), even following receipt of antiviral treatments and/or vaccines. Even after recovery from severe COVID-19, some patients have reported persistent symptoms that have been collectively referred to as long COVID, post-COVID-19, or post-acute sequelae of COVID-19 (PASC).

Long COVID may be defined in multiple ways, such as the presence of symptoms that have persisted beyond three weeks after initial symptom onset or the development of symptoms unexplained by an alternative diagnosis lasting for more than four weeks. The present study provides an overview of the current understanding of long COVID.

Epidemiology and risk factors of long COVID

A meta-analysis of 50 studies estimated the global prevalence of long COVID at 28 days or more to be 43%. Asia had the highest prevalence at 51%, followed by Europe and America.

Another meta-analysis reported that over 63% and 71% of patients had at least one post-COVID-19 symptom after 30 and 60 days post-onset/hospitalization, respectively. One study observed that the prevalence of long COVID among children and adolescents was 25.24%, whereas the rate of long COVID was 29.19% for hospitalized patients.

Furthermore, an Italian study revealed that long COVID prevalence in healthcare workers varied across COVID-19 pandemic waves. One United States study on veterans indicated that vaccine-breakthrough infections exhibited an elevated risk of post-acute sequelae, including gastrointestinal, cardiovascular, mental health, neurologic, and hematologic disorders. Another retrospective study identified age and severe disease as factors associated with a higher risk of experiencing at least three symptoms at one-year follow-up.

Clinical manifestations and mechanisms of long COVID

Long COVID can affect multiple organs, with one study concluding that respiratory, cardiovascular, and neuropsychological symptoms were most frequently reported in COVID-19 survivors. Numerous studies have identified fatigue as the most prevalent systemic symptom. Mood swings are most frequently reported in children and young adults.

Shortness of breath, post-activity polypnea, dyspnea, chest distress, pain while breathing, cough, and polypnea are common respiratory symptoms of long COVID. Common neurologic manifestations include brain fog, memory impairment, paresthesia, dysnomia, vertigo, headache, poor attention span, bradykinesia, anhedonia, and anguish.

In addition, psychosocial symptoms such as depression, anxiety, psychosis, post-traumatic stress disorder (PTSD), and behavioral disorder have also been reported. One meta-analysis observed anxiety and depression in 22% and 23% of long COVID patients, respectively. Memory loss/complaints, forgetfulness, and difficulty concentrating and sleeping were also prevalent in this study.

One study found elevated interleukin 2 (IL-2) and IL-17 levels, as well as reduced IL-4, IL-6, and IL-10 levels, in long COVID patients relative to those without any sequelae. Several biomarkers were found to be associated with neurologic sequelae, of which included angiotensin-converting enzyme 2 (ACE2), IL-17, transmembrane protease serine 2 (TMPRSS2), zonulin, and interferon (IFN)-γ.

The explicit mechanisms of long COVID remain poorly defined given its novelty. However, several mechanisms have been theorized, of which include damage to ACE2-expressing organs by SARS-CoV-2, inflammation due to persistent viral reservoir post-infection resolution, host responses such as over-production of cytokines, auto-immunity, and delayed inflammation resolution affecting homeostatic milieu of the organ(s), among others.

Vaccines, diagnosis, and potential treatment

One prospective case-control study reported that individuals were less likely to report persistent symptoms after receiving a second COVID-19 vaccine dose than non-vaccinated individuals. An Italian observational cohort study observed that BNT162b2 vaccination was associated with a lower prevalence of long COVID that decreased with the number of vaccine doses administered.

The appropriate diagnostic criteria for long COVID are unclear, as the condition can manifest with non-specific symptoms and involve multiple organ systems. Nevertheless, the diagnosis should be guided by the patient’s history, physical examination, and clinical manifestations. Functional status and quality of life can be assessed using a post-COVID-19 function status scale and patient-reported outcome measurement information system.

Montreal cognitive assessment, Compass 31, mini-mental status examination, and neurobehavioral system inventory may be used to evaluate neurologic conditions. Electrocardiograms, echocardiograms, pulmonary function tests, or chest radiography may be helpful for new cardiac or respiratory concerns.

Long COVID management warrants prompt a multi-disciplinary assessment that focuses on managing specific symptoms and supporting rehabilitation. Hyperbaric oxygen therapy (HBOT) is also a potential therapeutic modality.

Several trials are currently investigating the effects of physiotherapy, physical rehabilitation, neurorehabilitation, and cognitive interventions. These studies may provide more conclusive evidence in the future.

Concluding remarks

The number of long COVID cases may increase as the number of COVID-19 cases continues to rise worldwide. Based on currently available information, long COVID could develop in all COVID-19 patients, although severe patients are at an increased risk.

Furthermore, long COVID could present with heterogeneous clinical manifestations, with vaccination potentially being the only way to avert long COVID. Future studies are needed using established diagnostic and definition criteria to gain more insights into long COVID.

Journal reference:
  • Lai, C. C., Hsu, C. K., Yen, M. Y., et al. (2022). Long COVID: An inevitable sequela of SARS-CoV-2 infection. Journal of Microbiology, Immunology and Infection. doi:10.1016/j.jmii.2022.10.003

Study determines SARS-CoV-2 viability on food items at different temperatures

A recent Food Microbiology journal study explores the viability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on food items and what treatments may inactivate the virus from these products.

Study: Viability of SARS-CoV-2 on lettuce, chicken, and salmon and its inactivation by peracetic acid, ethanol, and chlorine dioxide. Image Credit: AstroStar / Shutterstock.com

Study: Viability of SARS-CoV-2 on lettuce, chicken, and salmon and its inactivation by peracetic acid, ethanol, and chlorine dioxide. Image Credit: AstroStar / Shutterstock.com

Background

SARS-CoV-2, the causative pathogen of the coronavirus disease 2019 (COVID-19) pandemic, is a betacoronavirus that primarily spreads through respiratory droplets and aerosols.

The seafood market in Wuhan, China, is considered the initial source of SARS-CoV-2. About 55% of China’s COVID-19 cases detected in December 2019 were associated with this market.

Several studies have linked other COVID-19 outbreaks with virus-contaminated frozen foods and food packaging materials. These observations have raised global concern over food safety during the pandemic.

In the current study, scientists assess the viability of SARS-CoV-2 on three food items stored at different temperatures. They also determine the potency of three disinfectants in inactivating the virus on food items.

Study design

Three food items were selected for the viral viability test: lettuce, chicken, and salmon. The food items were then contaminated with SARS-CoV-2 and stored at 20 °C (room temperature), 4 °C (refrigerated), and -40 °C (frozen).   

For the virus inactivation test, food-grade ethanol, chlorine dioxide, and peracetic acid were selected as disinfectants. Except for ethanol, which was used at 30%, 50%, and 70% concentrations, the other two disinfectants were used at three different concentrations, including the recommended concentration and half and twice the recommended concentration.

Viability of SARS-CoV-2 on food items

The lowest viability of SARS-CoV-2 on food items was observed at room temperature. No detectable viral titers were obtained on any food items after 48 hours of contamination. Among various food items, the highest half-life of SARS-CoV-2 was observed on salmon, followed by chicken and lettuce.

A significant induction in viability was observed at 4 °C. The highest viability at 4 °C was observed on salmon, where SARS-CoV-2 remained infectious for up to 14 days following contamination. On lettuce and chicken, SARS-CoV-2 remained detectable for up to 10 days.

A five- to nine-fold induction in the virus half-life was observed at 4 °C compared to that observed at room temperature. The highest half-life was observed on salmon, followed by chicken and lettuce.

At freezing temperatures, SARS-CoV-2 remained viable for up to four weeks on the tested food items. Significant induction of more than 30-fold in the viral half-life was also observed on each food item.

Inactivation of SARS-CoV-2 by disinfectants

Short-term exposure of one minute to 70% ethanol effectively inactivated SARS-CoV-2 on lettuce but failed to do the same on chicken and salmon. The inactivation of the virus on chicken and salmon was observed after a five-minute exposure to 70% ethanol.

No significant virus-inactivating effect was observed for chlorine dioxide at all tested concentrations and exposure periods. At the highest concentration and exposure time, chlorine dioxide was found to reduce viral infectivity to a certain level only on lettuce.

In contrast to chlorine dioxide, peracetic acid showed significantly higher potency in inactivating SARS-CoV-2 on food items. Specifically, peracetic acid completely inactivated the virus at twice the recommended concentration on each tested food item.

Study significance

The study findings indicate that the viability of SARS-CoV-2 on food items increases more than 30 times at freezing temperatures compared to room temperature. In addition to storage temperature, viral viability also depends on the type of food.

Two viral variants have been studied here, including SARS-CoV-2 S and SARS-CoV-2 L. SARS-CoV-2 L shows higher viability on food items than SARS-CoV-2 S. However, peracetic acid was identified as a highly effective disinfectant that can completely inactivate both viral variants on food items.

The highest potency of peracetic acid was observed at two times higher than the recommended concentration. However, no antiviral efficacy of chlorine-based disinfectants was observed in the study.

Journal reference:
  • Jung, S., Yeo, D., Wang, Z., et al. (2022). Viability of SARS-CoV-2 on lettuce, chicken, and salmon and its inactivation by peracetic acid, ethanol, and chlorine dioxide. Food Microbiology. doi:10.1016/j.fm.2022.104164