A survey and antibody test following the surge of SARS-CoV-2 Omicron infection in China (preprint)

The surge of SARS-CoV-2 Omicron infection in most Chinese residents at the end of 2022 provided a unique opportunity to understand how the immune system responds to the Omicron infection in a population with limited contact to prior SARS-CoV-2 variants. Moreover, whether the prototype SARS-CoV-2 booster vaccination could help induce the antibody against Omicron variants? Here, we tested the level of IgG, IgA, and IgM specific to the prototype SARS-CoV-2 spike RBD (Receptor Binding Domain) from the collected blood samples from 636 individuals. Sequential inoculation of different vaccines showed higher IgG levels after infection. As the antibody level against Omicron BA.5, BF.7, and XBB 1.5 of the individuals has highly positive correlation with the antibody level against prototype SARS-CoV2, the IgG level specific to the prototype SARS-CoV-2 spike RBD could also represent the IgG level against Omicron variants. Furthermore, the 4th booster vaccination could induce a comparable antibody level against prototype, Omicron BA.5, BF.7, and XBB 1.5 variants in the patients with 2 or 3-dose vaccination and protect people from being infected. In conclusion, these data suggest that the prototype SARS-CoV-2 booster vaccination helps induce a high level of antibody against prototype, BA.5, BF.7, and XBB 1.5 variants after Omicron infection.

A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2 (preprint)

Neutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC50) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 g of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.

Hetero-bivalent Nanobodies Provide Broad-spectrum Protection against SARS-CoV-2 Variants of Concern including Omicron (preprint)

Following Delta, Omicron variant triggered a new wave of SARS-CoV-2 infection globally, adaptive evolution of the virus may not stop, the development of broad-spectrum antivirals is still urgent. We previously developed two hetero-bivalent nanobodies with potent neutralization against original WT SARS-CoV-2, termed aRBD-2-5 and aRBD-2-7, by fusing aRBD-2 with aRBD-5 or aRBD-7, respectively. Here, we resolved crystal structures of these nanobodies in complex with RBD, and found the epitope of aRBD-2 differs from that of aRBD-5, aRBD-7. aRBD-2 binds to a conserved epitope which renders its binding activity to all variants of concern (VOCs) including Omicron. Interestingly, although monovalent aRBD-5 and aRBD-7 lost binding to some variants, they effectively improved the overall affinity when transformed into the hetero-bivalent form after being fused with aRBD-2. Consistent with the high binding affinities, aRBD-2-5-Fc and aRBD-2-7-Fc exhibited ultra-potent neutralization to all five VOCs; particularly, aRBD-2-5-Fc neutralized authentic virus of Beta, Delta and Omicron with the IC50 of 5.98~9.65 ng/mL or 54.3~87.6 pM. Importantly, aRBD-2-5-Fc provided in vivo prophylactic protection for mice against WT and mouse-adapted SARS-CoV-2, and provided full protection against Omicron in hamster model when administrated either prophylactically or therapeutically. Taken together, we found a conserved epitope on RBD, and hetero-bivalent nanobodies had increased affinity for VOCs over its monovalent form, and provided potent and broad-spectrum protection both in vitro and in vivo against all tested major variants, and potentially future emerging variants. Our strategy provides a new solution in the development of therapeutic antibodies for COVID-19 caused by newly emergent VOCs.

Transcriptome Profiling of Peripheral Blood Mononuclear Cells Reveals COVID-19 Patients Are Not Recovered to Normal After Discharge for 5 Months (preprint)

BackgroundHighly pathogenic coronavirus disease-2019 (COVID-19) initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has swiftly expanded throughout the world, and the fatality rate is still expanding due to the second wave in 2020 winters. This ongoing epidemic threatens public health with its new strain that emerged in some countries and might cause devastating deaths. Therefore, the host transcriptomic profile from patients during recovery is important for understanding this disease. MethodsWe performed transcriptome profiling of the RNAs isolated from the peripheral blood mononuclear cells (PBMCs) of recovered COVID-19 patients at hospital discharge of three months and five months respectively.ResultsOur results exposed diverse inflammatory genes and cytokine profiles to infection in recovered patients, and emphasize the highly expressed genes in COVID-19 patients like CCL4, CCL3, CXCL9, CXCL16, IL10, CSF2, VEGFA showed a decreasing trend in recovered patients. Furthermore, the integrated analysis predicted that JUN, CTSL, DDIT4, RRAS, BIRC5, CTSZ, CCNB2, CDK1, OAS1/2, IFIT3, RSAD2, and TP53I3 genes may be valuable for the recovery of COVID-19 patients. ConclusionsOur analysis confirms the presence of some inflammatory genes in recovered patients, suggesting COVID-19 patients did not return to their normal expression even after 5-months of discharge. Identification of transcriptome profiling of recovered patients provides useful information regarding its pathogenesis and might help for the development of better treatment for COVID-19.

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies and provides long-term protection against SARS-CoV-2 in rhesus macaques (preprint)

Coronavirus disease 2019 (COVID-19), which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, continues to threaten global public health. Developing a vaccine that only requires single immunization but provides long-term protection for the prevention and control of COVID-19 is important. Here, we developed an adeno-associated virus (AAV)-based vaccine expressing a stable receptor-binding domain (SRBD) protein. The vaccine requires only a single shot but provides effective neutralizing antibodies (NAbs) over 598 days in rhesus macaques (Macaca mulatta). Importantly, our results showed that the NAbs were kept in high level and long lasting against authentic wild-type SARS-CoV-2, Beta, Delta and Omicron variants using plaque reduction neutralization test. Of note, although we detected pre-existing AAV2/9 antibodies before immunization, the vaccine still induced high and effective NAbs against COVID-19 in rhesus macaques. AAV-SRBD immune serum also efficiently inhibited the binding of ACE2 with RBD in the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1/P.2 (Gamma), B.1.617.2 (Delta), B.1.617.1/3(Kappa), and C.37 (Lambda) variants. Thus, these data suggest that the vaccine has great potential to prevent the spread of SARS-CoV-2.

Potent in vitro Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain (preprint)

Cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KD ranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KD ranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KD of 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL ([~]0.043 nM) and 3.18 ng/mL ([~]0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnosis reagents for COVID-19. ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics including SARS-CoV-2 targeting antibodies remains critical. Due to their small size (13-15 kDa), highly solubility and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multi-valent formats, compared to the conventional antibody. Here, we report a serial of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.

Potential role of aberrant mucosal immune response to SARS-CoV-2 in pathogenesis of IgA Nephropathy (preprint)

Aberrant mucosal immunity has been suggested to play a pivotal role in pathogenesis of IgA nephropathy (IgAN), the most common form of glomerulonephritis worldwide. The outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal pathogen of coronavirus disease 2019 (COVID-19), has become a global concern. However, whether the mucosal immune response caused by SARS-CoV-2 influences the clinical manifestations of IgAN patients remains unknown. Here we tracked the SARS-CoV-2 anti-receptor binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the COVID-19 patients produced more SARS-CoV-2 anti-RBD IgA than IgG or IgM, and the levels of the IgA were stable during 4-41 days of infection. Among these IgA-dominated COVID-19 patients, we found a severe COVID-19 patient concurrent with IgAN. The renal function of the patient declined presenting with increased serum creatinine during the infection and till 7 months post infection. This patient predominantly produced anti-RBD IgA as well as total IgA in the serum compared to that of healthy controls. The analysis of the IgA-coated microbiota as well as proinflammatory cytokine IL-18, which was mainly produced in the intestine, reveals intestinal inflammation, although no obvious gastrointestinal symptom was reported. The mucosal immune responses in the lung are not evaluated due to the lack of samples from respiratory tract. Collectively, our work highlights the potential adverse effect of the mucosal immune response towards SARS-CoV-2, and additional care should be taken for COVID-19 patients with chronic diseases like IgAN.

Safety of reopening universities and colleges using a combined strategy during coronavirus disease 2019 in China: a cross-sectional study (preprint)

Background There is no consensus as to when and how to reopen schools during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate the safety of reopening universities and colleges using a combined strategy in China.Methods This cross-sectional study included 13,116 staffs and postgraduate students who have returned to the four campuses of the University of Science and Technology of China from 17 February (students returned from 12 May) to 2 July 2020. The returning to school was guided by a combined strategy including use of personal protective equipment, management of transportation, serological and nucleic acid tests for COVID-19, quarantine, and restrictions in and out of campus. Epidemiology history and COVID-19 related symptoms (fever, cough, and dyspnoea) were recorded in a subset of participants using an online questionnaire.Results Among 13,116 participants, 4067 tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid and no positive results were identified. Of 9049 participants who chose to conduct antibody tests, 28 (0.3%) tested positive but no one was confirmed by the additional viral nucleic acid tests. Online questionnaires were collected from 5741 participants (mean 25.1 years, 35% female). High-risk exposures and COVID-19 related symptoms were reported in 8.3% and 7.4% of participants, respectively. Comorbidities (hypertension, diabetes, chronic pulmonary disease, and chronic kidney disease) were rare (0.2%-1.5%). Conclusions Using a combined strategy for COVID-19 prevention and control, safely reopening of universities and colleges in low-risk regions is possible and laboratory screening for SARS-CoV-2 infection may not be necessary. Further studies need to cautiously evaluate the safety of reopening schools, if any, in the middle- and high-risk regions.

Safety of Reopening Universities and Colleges Using a Combined Strategy During Coronavirus Disease 2019 in China: Cross Sectional Study (preprint)

Background: There is no consensus as to when and how to reopen schools during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate the safety of reopening universities and colleges using a combined strategy in China.Methods: This cross-sectional study included 13,116 staffs and postgraduate students who have returned to the four campuses of the University of Science and Technology of China from 17 February (students returned from 12 May) to 2 July 2020. The returning to school was guided by a combined strategy including use of personal protective equipment, management of transportation, serological and nucleic acid tests for COVID-19, quarantine, and restrictions in and out of campus. Epidemiology history and COVID-19 related symptoms (fever, cough, and dyspnoea) were recorded in a subset of participants using an online questionnaire.Findings: Among 13,116 participants, 4067 tested for SARS-CoV-2 nucleic acid and no positive results were identified. Of 9049 participants who chose to conduct antibody tests, 28 (0.3%) tested positive but no one was confirmed by the additional viral nucleic acid tests. Online questionnaires were collected from 5741 participants (mean 25.1 years, 35% female). High-risk exposures and COVID-19 related symptoms were reported in 8.3% and 7.4% of participants, respectively. Comorbidities (hypertension, diabetes, chronic pulmonary disease, and chronic kidney disease) were rare (0.2%-1.5%). Interpretation: Using a combined strategy for COVID-19 prevention and control, safely reopening of universities and colleges in low-risk regions is possible and laboratory screening for SARS-CoV-2 infection may not be necessary. Further studies need to cautiously evaluate the safety of reopening schools, if any, in the middle- and high-risk regions.Funding: This research received grants from the Fundamental Research Funds for the Central Universities (Grant number: YD9110002008, YD9110004001, and YD9110002002).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: All participants who participated the online survey provided informed consent. Informed consent was waived for other participants as this study did not collect their individual data. This study was approved by the Research Ethics Commissions of the First Affiliated Hospital of USTC.

Decline of SARS-CoV-2 specific IgG, IgM and IgA in convalescent COVID-19 patients within 100 days after hospital discharge (preprint)

Monitoring the levels of SARS-CoV-2 specific antibodies such as IgG, M and A in COVID-19 patient is an alternative method for diagnosing SARS-CoV-2 infection and an simple way to monitor immune responses in convalescent patients and after vaccination. Here, we assessed the levels of SARS-CoV-2 RBD specific antibodies in twenty-seven COVID-19 convalescent patients over 28-99 days after hospital discharge. Almost all patient who had severe or moderate COVID-19 symptoms and a high-level of IgG during the hospitalization showed a significant reduction at revisit. The remaining patients who had a low-level IgG during hospitalization stayed low at revisit. As expected, IgM levels in almost all convalescent patients reduced significantly or stayed low at revisit. The RBD-specific IgA levels were also reduced significantly at revisit. We also attempted to estimate decline rates of virus-specific antibodies using a previously established exponential decay model of antibody kinetics after infection. The predicted days when convalescent patients' RBD-specific IgG reaches to an undetectable level are approximately 273 days after hospital discharge, while the predicted decay times are 150 days and 108 days for IgM and IgA, respectively. This investigation and report will aid current and future studies to develope SARS-CoV-2 vaccines that are potent and long-lasting.

Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA (preprint)

The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis, is associated with multiple inflammation diseases5. It's possible that SARS-CoV-2 infection may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.

Association of Personal Protective Equipment Use with Successful Protection Against COVID-19 Infection Among Health Care Workers (preprint)

The coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. In order to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs, we conducted a molecular epidemiological study among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. Nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) detection were performed to confirm SARS-CoV-2 infection among those HCWs. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 15, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. These HCWs were provided with adequate supply of PPE as committed by their original institutions or provinces. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. In conclusion, our findings indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection.

COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by a quantitative and sensitive immunoassay (preprint)

Background. The pandemic of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing great loss. Detecting viral RNAs is standard approach for SARS-CoV-2 diagnosis with variable success. Currently, studies describing the serological diagnostic methods are emerging, while most of them just involve the detection of SARS-CoV-2-specific IgM and IgG by ELISA or flow immunoassay with limited accuracy. Methods. Diagnostic approach depends on chemiluminescence immunoanalysis (CLIA) for detecting IgA, IgM and IgG specific to SARS-CoV-2 nucleocapsid protein (NP) and receptor-binding domain (RBD) was developed. The approach was tested with 216 sera from 87 COVID-19 patients and 483 sera from SARS-CoV-2 negative individuals. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) analysis. Concentration kinetics of RBD-specific serum antibodies were characterized. The relationship of serum RBD-specific antibodies and disease severity was analyzed. Results. The diagnostic accuracy based on RBD outperformed those based on NP. Adding IgA to a conventional serological test containing IgM and IgG improves sensitivity of SARS-CoV-2 diagnosis at early stage. CLIA for detecting RBD-specific IgA, IgM and IgG showed diagnostic sensitivities of 98.6%, 96.8% and 96.8%, and specificities of 98.1%, 92.3% and 99.8%, respectively. Median concentration of IgA and IgM peaked during 16-20 days after illness onset at 8.84 g/mL and 7.25 g/mL, respectively, while IgG peaked during 21-25 days after illness onset at 16.47 g/mL. Furthermore, the serum IgA level positively correlates with COVID-19 severity. Conclusion. CLIA for detecting SARS-CoV-2 RBD-specific IgA, IgM and IgG in blood provides additional values for diagnosing and monitoring of COVID-19.

Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis (preprint)

ABSTRACTDespite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.Competing Interest StatementJingwen Fang is the executive officer of HanGen BiotechView Full Text

Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China (preprint)

The outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.