05 August, 2021

An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19 -

Background Both continuous positive airway pressure (CPAP) and high-flow nasal oxygenation (HFNO) have been recommended for acute respiratory failure in COVID-19. However, uncertainty exists regarding effectiveness and safety. Methods In the Recovery- Respiratory Support multi-center, three-arm, open-label, adaptive, randomized controlled trial, adult hospitalized patients with acute respiratory failure due to COVID-19, deemed suitable for treatment escalation, were randomly assigned to receive CPAP, HFNO, or conventional oxygen therapy. Comparisons were made between each intervention and conventional oxygen therapy. The primary outcome was a composite of tracheal intubation or mortality within 30-days. Results Over 13-months, 1272 participants were randomized and included in the analysis (380 (29.9%) CPAP; 417 (32.8%) HFNO; 475 (37.3%) conventional oxygen therapy). The need for tracheal intubation or mortality within 30-days was lower in the CPAP group (CPAP 137 of 377 participants (36.3%) vs conventional oxygen therapy 158 of 356 participants (44.4%); unadjusted odds ratio 0.72; 95% CI 0.53 to 0.96, P=0.03). There was no difference between HFNO and conventional oxygen therapy (HFNO 184 of 414 participants (44.4%) vs conventional oxygen therapy 166 of 368 participants (45.1%); unadjusted odds ratio 0.97; 95% CI 0.73 to 1.29, P=0.85). Conclusions CPAP, compared with conventional oxygen therapy, reduced the composite outcome of intubation or death within 30 days of randomisation in hospitalized adults with acute respiratory failure due to COVID-19. There was no effect observed, compared with conventional oxygen therapy, with the use of HFNO. (Funded by the UK National Institute for Health Research; ISRCTN 16912075).

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Two-dimensional multiplexed assay for rapid and deep SARS-CoV-2 serology profiling and for machine learning prediction of neutralization capacity -

Antibody responses serve as the primary protection against SARS-CoV-2 infection through neutralization of viral entry into cells. We have developed a two-dimensional multiplex bead binding assay (2D-MBBA) that quantifies multiple antibody isotypes against multiple antigens from a single measurement. Here, we applied our assay to profile IgG, IgM and IgA levels against the spike antigen, its receptor-binding domain and natural and designed mutants. Machine learning algorithms trained on the 2D-MBBA data substantially improve the prediction of neutralization capacity against the authentic SARS-CoV-2 virus of serum samples of convalescent patients. The algorithms also helped identify a set of antibody isotype-antigen datasets that contributed to the prediction, which included those targeting regions outside the receptor-binding interface of the spike protein. We applied the assay to profile samples from vaccinated, immune- compromised patients, which revealed differences in the antibody profiles between convalescent and vaccinated samples. Our approach can rapidly provide deep antibody profiles and neutralization prediction from essentially a drop of blood without the need of BSL-3 access and provides insights into the nature of neutralizing antibodies. It may be further developed for evaluating neutralizing capacity for new variants and future pathogens.

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A Master Autoantigen-ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases -

Chronic and debilitating autoimmune sequelae pose a grave concern for the post-COVID-19 pandemic era. Based on our discovery that the glycosaminoglycan dermatan sulfate (DS) displays peculiar affinity to apoptotic cells and autoantigens (autoAgs) and that DS-autoAg complexes cooperatively stimulate autoreactive B1 cell responses, we compiled a database of 751 candidate autoAgs from six human cell types. At least 657 of these have been found to be affected by SARS-CoV-2 infection based on currently available multi-omic COVID data, and at least 400 are confirmed targets of autoantibodies in a wide array of autoimmune diseases and cancer. The autoantigen-ome is significantly associated with various processes in viral infections, such as translation, protein processing, and vesicle transport. Interestingly, the coding genes of autoAgs predominantly contain multiple exons with many possible alternative splicing variants, short transcripts, and short UTR lengths. These observations and the finding that numerous autoAgs involved in RNA-splicing showed altered expression in viral infections suggest that viruses exploit alternative splicing to reprogram host cell machinery to ensure viral replication and survival. While each cell type gives rise to a unique pool of autoAgs, 39 common autoAgs associated with cell stress and apoptosis were identified from all six cell types, with several being known markers of systemic autoimmune diseases. In particular, the common autoAg UBA1 that catalyzes the first step in ubiquitination is encoded by an X-chromosome escape gene. Given its essential function in apoptotic cell clearance and that X-inactivation escape tends to increase with aging, UBA1 dysfunction can therefore predispose aging women to autoimmune disorders. In summary, we propose a model of how viral infections lead to extensive molecular alterations and host cell death, autoimmune responses facilitated by autoAg-DS complexes, and ultimately autoimmune diseases. Overall, this master autoantigen-ome provides a molecular guide for investigating the myriad of autoimmune sequalae to COVID-19 and clues to the rare but reported adverse effects of the currently available COVID vaccines.

🖺 Full Text HTML: A Master Autoantigen-ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases

Shocked, relaxed, tired: Mental health during the three waves of the Covid-19 -

Background: Several recent studies reported that Covid-19 pandemic induces significant mental distress. It remains unknown, however, whether mental distress persists or undergoes extinction in response to consecutive Covid-19 waves. We here examine mental distress prior to and across the three Covid-19 waves. Methods: We measured stress and depressive symptoms prior to and across the three Covid-19 waves in a well-established population-based sample. A total of 330 participants completed e-questionnaires prior to and during the Covid-19 waves. Friedman9s repeated-measures and Wilcoxon rank sum pairwise test with Bonferroni correction were used to investigate repeated-measure differences, while the Kruskal-Wallis test was used to assess the effect of behavioral and physiological parameters on mental health. Results: We found significantly increased mental distress during each of the Covid-19 waves compared with the pre- Covid-19 period. Increased mental distress was more common in women and most pronounced during the 1st and in particular, the 3rd Covid-19 wave. The stress and depressive symptoms increased during pandemic compared with the pre- Covid-19 period by a maximum of 1.58 and 3.63 times, respectively. Negative emotions and loneliness were identified as the most significant risk factors of Covid-19-induced mental distress, while resilience was found to be protective. Conclusions: Mental distress surged during all the Covid-19 waves without showing extinction. This pattern is mechanistically reminiscent of the post-traumatic stress disorder. Our results suggest that the Covid-19 pandemic underlies development of a novel chronic mental health disorder and do not exclude possible further deterioration of mental health in case of future Covid-19 waves.

🖺 Full Text HTML: Shocked, relaxed, tired: Mental health during the three waves of the Covid-19

Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada -

Background: The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants), and then by the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented but data for increased virulence is limited. We used Ontario COVID-19 case data to evaluate the virulence of these VOCs compared to non-VOC SARS-CoV-2 infections, as measured by risk of hospitalization, intensive care unit (ICU) admission, and death. Methods: We created a retrospective cohort of people in Ontario testing positive for SARS31 CoV-2 and screened for VOCs, with dates of test report between February 7 and June 27, 2021 (n=212,332). We constructed mixed effects logistic regression models with hospitalization, ICU admission, and death as outcome variables. Models were adjusted for age, sex, time, vaccination status, comorbidities, and pregnancy status. Health units were included as random intercepts. Results: Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (43-62%) for hospitalization; 89% (67-116%) for ICU admission; and 51% (30-74%) for death. Increases with Delta variant were more pronounced: 108% (80-138%) for hospitalization; 234% (164-331%) for ICU admission; and 132% (47-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-2 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred in the absence of VOC emergence.

🖺 Full Text HTML: Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada

RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from asymptomatic and symptomatic individuals -

To validate an improved sample preparation method for extraction free Direct RT-LAMP and define the clinical performance of four different RT-LAMP assay formats for detection of SARS-CoV-2 with a multisite clinical evaluation. We describe Direct RT-LAMP on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples collected from asymptomatic and symptomatic individuals across multiple healthcare and community settings. For Direct RT-LAMP, we found a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) of 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT-qPCR ORF1ab CT values of<25 and <33 (high and medium-high viral copy number, respectively), we found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) and 87.32% (80.71-92.31%) for saliva. For RNA RT-LAMP DSe and DSp were 95.98% (92.74-98.06%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. The findings from these evaluations demonstrate that RT-LAMP testing of swabs and saliva is applicable to a variety of different use-cases, including frequent, interval-based testing of saliva from asymptomatic individuals via Direct RT-LAMP that may otherwise be missed using symptomatic testing alone.

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Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level -

Background: Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over-time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally. Methods: Deep sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome. Results: Sequence analysis suggests that the three adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS) rather than by stepwise mutation. The resulting sequence changes generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain of nucleocapsid. Deep sequencing data from 981 clinical samples confirmed the presence of the novel TRS-CS-dimerization domain RNA in individuals with the K203/R204 variant. Quantification of sub-genomic RNA indicates that viruses with the K203/R204 variant may also have increased expression of sub-genomic RNA from other open reading frames. Conclusions: The finding that homologous recombination from the TRS may have occurred since the introduction of SARS-CoV-2 in humans resulting in both coding changes and novel sub-genomic RNA transcripts suggests this as a mechanism for diversification and adaptation within its new host.

🖺 Full Text HTML: Generation of a novel SARS-CoV-2 sub- genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level

A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination -

Summary Background: The emerging threat represented by SARS–CoV–2 variants, demands the development of therapies for better clinical management of COVID–19. MAD0004J08 is an extremely potent Fc-engineered monoclonal antibody (mAb) able to neutralise in vitro all current SARS–CoV–2 variants of concern (VoCs). This ongoing study, evaluates safety, pharmacokinetics and SARS–CoV–2 sera neutralization effect of MAD0004J08 when administered as single dose intramuscularly in healthy adults. Method: We conducted a dose escalation study with sequential enrolment of three cohorts, each with an increasing dose level of MAD0004J08 (48mg, 100mg and 400mg). Within each cohort, 10 young healthy adults were randomized with 4:1 ratio to a single intramuscular (i.m.) injection of MAD0004J08 or placebo. The primary endpoint is the proportion of subjects with severe and/or serious treatment emergent adverse events (TEAEs) within 7 days post–treatment. Secondary endpoints reported in this paper are the proportion of subjects with solicited TEAEs up 7 days post dosing, MAD0004J08 serum concentrations and neutralising activity versus the original SARS-COV-2 Wuhan virus at different timepoints post-dosing. As post-hoc analyses, we compared the sera neutralising titres of subjects who received MAD0004J08 with those of people that had received the COVID–19 BNT162b2 mRNA vaccine in the previous sixty days (n=10) and COVID-19 convalescent patients (n=20), and assessed serum neutralisation activity against the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS–CoV–2 variants of concern. Findings: A total of 30 subjects, 10 per cohort, were enrolled and randomized. Data up to 30 days were available and analysed in this report. No severe TEAEs were reported in any of the cohorts in the 7 days post-treatment. MAD0004J08 was detected in the sera of treated subjects within few hours post-administration and reached almost maximal levels on day 8. The geometric mean neutralising titres (GMT) assessed against the original Wuhan virus peaked on day 8 and ranged 226 – 905, 905 – 2,560, and 1,280 – 5,120 for cohort 1, 2 and 3 respectively. The sera neutralising GMT in MAD0004J08 treated subjects in all the three cohorts were found to be 1·5– 54·5–fold higher compared to sera from convalescent patients and 1·83– 76·4–fold higher compared to sera from COVID-19 vaccinees. Finally, GMT in MAD0004J08 treated subjects showed high neutralising titres versus the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS-CoV-2 VoCs. Interpretation: A single dose administration of MAD0004J08 via i.m. route is safe and well tolerated and results in a rapid systemic distribution of the MAD0004J08 and sera neutralising titres higher than COVID–19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralise major SARS–CoV–2 variants of concern. Based on these results, a Phase 2-3 trial is ongoing to further assess the safety, dosage, and efficacy of MAD0004J08 in asymptomatic or mild-moderate symptomatic COVID–19 patients. Funding: EU Malaria Fund, Ministero dello Sviluppo Economico, Ministero della Salute, Regione Toscana, Toscana Life Sciences Sviluppo and European Research Council.

🖺 Full Text HTML: A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination

Domestic and international mobility trends in the United Kingdom during the COVID-19 pandemic: An analysis of Facebook data -

Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which resulted in changes to mobility across different regions. An understanding of how these policies impacted travel patterns over time and at different spatial scales is important for designing effective strategies, future pandemic planning and in providing broader insights on the population geography of the country. Crowd level data on mobile phone usage can be used as a proxy for population mobility patterns and provide a way of quantifying in near- real time the impact of social distancing measures on changes in mobility. Here we explore patterns of change in densities, domestic and international flows and co-location of Facebook users in the UK from March 2020 to March 2021. We find substantial heterogeneities across time and region, with large changes observed compared to pre-pandemic patterns. The impacts of periods of lockdown on distances travelled and flow volumes are evident, with each showing variations, but some significant reductions in co-location rates. Clear differences in multiple metrics of mobility are seen in central London compared to the rest of the UK, with each of Scotland, Wales and Northern Ireland showing significant deviations from England at times. Moreover, the impacts of rapid changes in rules on international travel to and from the UK are seen in substantial fluctuations in traveller volumes by destination. While questions remain about the representativeness of the Facebook data, previous studies have shown strong correspondence with census-based data and alternative mobility measures, suggesting that findings here are valuable for guiding strategies.

🖺 Full Text HTML: Domestic and international mobility trends in the United Kingdom during the COVID-19 pandemic: An analysis of Facebook data

Prospective cohort study of socioeconomic status and subsequent unemployment under COVID-19 in Japan -

Background: This study examined the relationship between socioeconomic status (SES) and subsequent unemployment. Methods: This prospective cohort study was conducted using a self-administrated questionnaire in Japan. SES, personal characteristics, and occupation of recruited workers were surveyed at baseline (December 22-25, 2020); subsequent unemployment was examined at follow-up (February 18-19, 2021). We determined the odds ratios (ORs) of unemployment for SES and other variables using a multilevel logistic model. Results: Among all 19,941 participants, 2.3% reported experience of unemployment through negative reasons. Multivariate analysis showed the OR and 95% confidence interval for unemployment associated with age to be 0.66 (0.47-0.92) for 30-39 years, 0.36 (0.25-0.51) for 40-49, 0.36 (0.25-0.53) for 50-59, and 0.43 (0.27-0.67) for more than 60 compared with 20-29 years. The association with annual household income was 2.96 (1.94-4.50) for <2 million yen and 1.51 (1.03-2.22) for 2-4 million yen compared with >10 million yen. The association with marital status was 1.43 (1.04-1.98) for bereaved/divorced compared with married (working spouse). The association with occupation was 1.75 (1.35-2.29) for temporary or contract employees and 2.11 (1.04-4.30) for agriculture, forestry, or fishing compared with general employees. The association with job type was 1.69 (1.34-2.15) for mainly manual labor. Conclusion: We observed a relationship between SES and subsequent unemployment under COVID-19. It is necessary to provide broad, ongoing support in the form of both short-term assistance and long-term job training and health care.

🖺 Full Text HTML: Prospective cohort study of socioeconomic status and subsequent unemployment under COVID-19 in Japan

Design, immunogenicity and efficacy of a Pan-SARS-CoV-2 synthetic DNA vaccine -

Here we have employed SynCon(R) design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT- matched vaccines.

🖺 Full Text HTML: Design, immunogenicity and efficacy of a Pan-SARS-CoV-2 synthetic DNA vaccine

SARS-CoV-2 antibody binding and neutralization in dried blood spot eluates and paired plasma -

Widescale assessment of SARS-CoV-2-specific antibodies is critical to understanding population seroprevalence, correlates of protection, and the longevity of vaccine-elicited responses. Most SARS-CoV-2 studies characterize antibody responses in plasma/sera. While reliable and broadly used, these samples pose several logistical restrictions such as requiring venipuncture for collection and cold chain for transportation and storage. Dried blood spots (DBS) overcome these barriers as they can be self-collected by fingerstick and mailed and stored at ambient temperature. Here, we evaluate the suitability of DBS for SARS-CoV-2 antibody assays by comparing several antibody responses between paired plasma and DBS from SARS-CoV-2 convalescent and vaccinated individuals. We found that DBS not only reflected plasma antibody binding by ELISA and epitope profiles using phage-display, but also yielded SARS-CoV-2 neutralization titers that highly correlated with paired plasma. Neutralization measurement was further streamlined by adapting assays to a high-throughput 384-well format. This study supports the adoption of DBS for numerous SARS-CoV-2 binding and neutralization assays.

🖺 Full Text HTML: SARS-CoV-2 antibody binding and neutralization in dried blood spot eluates and paired plasma

SARS-CoV-2 viral load monitoring by extraction-free testing of saliva -

Real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) remains the foundation of SARS- CoV-2 testing due to its accessibility, scalability, and superior assay performance. Variability in specimens and methods prevent standardization of RT-qPCR assays and reliable quantitative reporting to assess viral load. We developed an extraction-free RT-qPCR assay for detection of SARS-CoV-2 in saliva and monitored viral load until convalescence in COVID-19 patients. Comparison of 231 matched anterior nares swab and saliva specimens demonstrated that extraction-free testing of saliva has equivalent analytical and clinical assay performance compared to testing of RNA extracts from either anterior nares or saliva specimens. Analysis of specimen pairs revealed higher viral loads in the nasal cavity compared to the oral cavity, although this difference did not impact clinical sensitivity for COVID-19. Extraction-free testing of a combination specimen consisting of both nasal swab and saliva is also demonstrated. Assessment of viral load by RT-qPCR and parallel digital droplet PCR (ddPCR) revealed that cycle threshold (Ct) values less than approximately 30 correlated well with viral load, whereas Ct values greater than 30 correspond to low viral loads <10 copies/uL. Therefore, extraction-free saliva testing maximizes testing efficiency without compromising assay performance and approximates viral loads >10 copies/uL. This technology can facilitate high-throughput laboratory testing for SARS-CoV-2, monitor viral load in individual patients, and assess efficacy of therapies for COVID-19.

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COVID19 vaccine type and humoral immune response in patients receiving dialysis -

Background Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination. Methods We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined no seroconversion as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as no RBD IgG response, and a semiquantitative RBD IgG index value <10 as diminished RBD IgG response Results Of the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination. Conclusions One in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

🖺 Full Text HTML: COVID19 vaccine type and humoral immune response in patients receiving dialysis

Lymphocyte count is a universal predictor to the health status and outcomes of patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-regression analysis -

Background This study aimed to evaluate the prediction capabilities of clinical laboratory biomarkers to the prognosis of COVID-19 patients. Methods Observational studies reporting at least 30 cases of COVID-19 describing disease severity or mortality were included. Meta-data of demographics, clinical symptoms, vital signs, comorbidities, and 14 clinical laboratory biomarkers on initial hospital presentation were extracted. Taking the outcome group as the analysis unit, meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. The unadjusted effect of each potential predictor of the three binary outcome variables (i.e., severe vs. non-severe, critically severe vs. non-critically severe, and dead vs. alive) was examined one by one by fitting three series of simple GEE logistic regression models due to missing data. The worst one was dropped one at a time. Then, a final multiple GEE logistic regression model for each of the three outcome variables was obtained. Findings Meta-data was extracted from 76 articles, reporting a total of 26,627 cases of COVID-19. Patients were recruited across 16 countries. The number of studies (patients) included in the final models of the analysis for severity, critical severity, and mortality was 38 studies (9,764 patients), 21 studies (4,792 patients), and 24 studies (14,825 patients), respectively. After adjusting for the effect of age, lymphocyte count mean or median ≤ 1.03 (estimated hazard ratio [HR] = 46.2594, p < 0.0001), smaller lymphocyte count mean or median (HR < 0.0001, p = 0.0028), and lymphocyte count mean or median ≤ 0.8714 (HR = 17.3756, p = 0.0079) were the strongest predictor of severity, critical severity, and mortality, respectively. Interpretation Lymphocyte count should be closely watched for COVID-19 patients in clinical practice. Keywords Laboratory data, lymphocyte, logistic regression analysis, clustered data, GEE.

Covid-19 Sentry

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